I am left handed and have always used computer mice set in the right-handed orientation. As a result I hold the mouse at a kind of angle in my palm, and it feels like the most natural way to hold it. If I attempt to hold the mouse level with my hand it looks and feels wrong.
I did a :smack: when I realized that it would be unfeasable to switch the orientation around considering that most of the users are right handed and that I use several computers at work all of which are used often by others, so (long sentence getting longer) I must have become this way by conceding to the right handers and then forgot and thought it was always the case.
Being a Mac user with an old-fogey ADB PowerBook, I still have a one-button mouse.
While right handed I swapped the mouse to my left hand some years ago. This was due to some overuse problems, but I’ve since heard this is better for you anyway, as the right side of a keyboard is further way from the ideal spot for the mouse to be due to the numeric keypad.
Anyway, having swapped the mouse over I kept the buttons in the normal configuration. It took me less than a day to get accustomed to it, despite being *very *right handed.
I’m comfortable going either way. At home I use my left hand and and have the mouse configured for the right button. At work I leave the mouse the way it is and use my right hand and left button since I am usually the only lefty around. Actually I really don’t have a preference when it comes to how the mouse is configured or which hand I use.
I’m a purist–I switch the buttons AND move the whole mouse to the left side of the keyboard. I don’t know how many times I’ve had cow-orkers and family trying something on my computer, with me at their shoulder saying “Left-handed mouse, left-handed mouse!” They all giggle at how unnatural it feels. I say, let them live in our world for a second. 
I put it on the left hand side, with the buttons set for left-handed, but I’m a righty. I want the area to the right-hand side of the keyboard free for writing on.
That means that when someone else tries to use my computer at work, they inevitably say, “oh, you’re left-handed” and I say “no, I’m right-handed” and then they look at me strangely and hurry up and do whatever it is is that they want to use my computer for.
I am left-handed but have always used my mouse just as a right-handed person would. Never thought to have it any other way because it just seems natural. It is nice to have the left hand free to jot something down if needed and not have to move my hand from mouse to pen to paper and back to mouse.
When I learned 10-key I made sure to learn it with my right hand so my left hand was free to write down the numbers I was adding.
When I do try to use the mouse with my left hand it feels, well, unnatural.
Another leftie who leaves the mouse on the right side and just learned to deal with it.
My friend is a leftie and switched the touchpad key settings on her laptop. It confused the Hell out of me when my right-handed self became her unofficial extra roommate last semester.
I’m like you, Lobsang. I’m a lefty uses my left hand, but hasn’t changed the button configuration. So, I also hold it at an angle, with the left side of the mouse going down the palm of my hand, and I click with my middle finger. It’s easiest that way, so when I have to help someone with their computer at work, all I have to do is move the mouse to the left.
Well, this is nearly word for word what I was going to write. I think it gives lefties a bit of an advantage since we don’t have to go back and forth picking up and putting down our pens.
I’m just like AndrewT: I’m firmly right-handed, but I switched the mouse on my PC at work to the left side because I was noticing some mouse fatigue in my right hand. I have two computers at my desk, one PC and one Mac, so the original idea was to have one left-handed and the other right-handed to break up the strain on one hand. However, I now do almost no work on the Mac (not by choice; I much prefer Macs personally), so it works out as lefty at work, righty at home. Like Lobsang, when using the PC, I hold the mouse at an angle so my left index finger rests on the left button.
I’m severely lefty. So severely that I can’t do my hair on the right side. 
But I’ve adjusted to righty-mouse use, and I honestly can’t use my left for it without accidentally right-clicking all over the place. I guess if I set the buttons to lefty configuration it would be easier, but I’ve got too many computers I use at work to bother, and I can’t have it different at home.
I started out using my mouse on the left side with the right-handed configuration (used my ring finger for clicking) but a severe case of Mouse Elbow made it necessary for me to switch my mouse to the right and deal with it. Put me in the ranks with the lefties who now think it feels weird to have the mouse on the left side.
I’m left handed, and my mouse is on the left side of the keyboard, but in the standard right-handed button configuration. I’ve been using mice seemingly since the day they were invented, which means for a sizeable part of my mousing life, it was challenging, if not impossible, to swap the button arrangements, let alone move the mouse from one side of the keyboard to the other, if there wasn’t enough slack in the cable.
Now, I’m going around from desk to desk helping users that it would take half my day if I had to switch from left-handed buttons to right-handed buttons.
One of my users is left-handed and uses left-handed buttons. Screws me up good and well every time I’m working on her PC.
I’m ambimousterous at work. At home I use a pen and tablet.
I’m extremely left-handed. Nevertheless, I don’t think it matters when it comes to learning something new, and developing muscle memory. It’s such a right-handed world that I do a multitude of delicate motor tasks right handed (just not things like writing). I used to do data entry (10 key) right handed, and was the fastest of several hundred people. I could never dial a rotary phone left handed either.
As for the mouse, I’m the same as the OP. The only concession to my left handedness is that the mouse is on the left of my keyboard and I actually use my left hand. Apart from that, I use the right-hand-configured-mouse-at-an-angle approach. It feels more comfortable than doing it the left handed way (which I have tried). I’m not going to doom myself to having to spend time in the control panel on every occasion I use somebody else’s computer for the rest of my life.
It is such an overwhelmingly right handed world that even I as a lefty tend to not think about it much, so I can’t really blame the righties for not giving us a thought. Mostly, I’ve adapted. On some occasions, it’s a positive advantage (ATM keys on the right - left hand free to piledrive Mr Mugger). There are occasions though when it is a total piss off. A main one of these would be signing a register or a guest book at a party or a private club. You just have to hope you’re presented with the left page, because they all open with the binding facing left, and if you get the right page there’s a huge bulge of used pages which you have to somehow manage to get your pen around.
I am firmly left-handed but I can switch between mouse configurations with ease. Working the reference desk, I share computers with several co-workers and it’s not worth the trouble to switch the buttons. Besides, the whole desk and position of computers is set up for right-handers.
But in my work office, my desk and computer is all lefty. A side benefit is that co-workers tend to not pop in to “borrow” my desk or computer.
At home, my computer, desk, chair, in fact, the whole room is set up left-handed. I get a smug little pleasure on the rare occassions when a right-hander has to struggle with it.
I think us left-handers are all ambidextrous to a degree because we have to be. My parents learned when I was just a tyke that the best way to teach me how to do something was to show me their right-handed way and let me decide if and how I wanted to turn it around. This worked well except I still tie the most sideways awful-looking bow!
lefty mouse at work, use either hand depending on the need to write. yes, i have to mention “it’s a lefty!” if someone want to use it.
mac at home.
I, too, am mostly right-handed and moved the mouse to the left side yonks ago. I found it to be more efficient to move the cursor with the mouse with my left hand and enter data using the keypad with my right hand. Unfortunately my new job requires a lot of meticulous CAD drawing, and I think I’m getting carpal tunnel syndrome; so I’ve moved the mouse over to the eight side at work. I still use the mouse on my left side at home, but I’m trying to train myself to use my index finger instead of my middle finger.