I am replaying Fallout again. But this time, I am trying to play with a left-handed mouse. However, the game does not seem to honor the windows settings, and keeps using the right-handed button assignments.

I have checked the .ini files, and the options settings, but no luck.

Any ideas?

Try contacting Timeslip, maybe she knows what to do. I would search for her in NMA, because she rarely post here.

You can do this with Timeslip's sfall (for Fo2):

* Open ddraw.ini in notepad
* Search for:
;Set to 1 to reverse the left and right mouse buttons
ReverseMouseButtons=0
* Change to 1
* Play

Unfortunately, this is for Fallout 2, so like I said, you better contact her.