The safety can be moved into the off position, it gets bumped by a seat belt etc. A step in safeguarding this from occurring is to have a holster that it molded in such a fashion that the thumb safety "rests" in a spot that prevents it from moving.
Another option is trimming off the right side lever so that it doesn't stick out as much or replace the ambi with a lower profile part such as THIS.
When I carried a 1911 with an ambi, there were a couple times I'd find it in the off position, this really didn't bother me as there was still the grip safety, firing pin safety, and a pull of the trigger that had be be dealt with before the gun would go off, this was also with a holster that did not have a molded body panel to help prevent the safety from moving. I will also add that during that time I was in/out of the car alot and that I don't recall the safety ever being switched off during more normal activities.
If I do add an ambi in the future, I plan on buying one of the above listed safeties and mating it with an elongated left side lever to have the best of both worlds, a long lever for right handed use, and a low profile lever for left handed use should the need arise without the worry of anything catching on the safety.