With the amount of US-produced TV and movies shown in the English-speaking world, I'd be surprised if there were many Americanisms which would not be understood. Sure, there would be regional words or expressions, but they would likely not be understood by the majority of Americans, let alone the rest of the world.
To use an example from this thread, way before I ever visited the States I knew that a Drug Store was what I would call a Chemist. I've been to the US many times and I don't recall ever having a problem understanding anything. The closest thing would be mundane stuff unlikely to have come up in movies or TV shows. For example, I still don't know whether "half-and-half" milk is what we in Australia would call "full cream" milk, but that's about the extent of my misunderstanding of American words.
The opposite of course is much more problematic. I have to be very careful what I say in the US, otherwise if I accidentally use Australian expressions or words I will frequently not get my message across.