Depends what you are talking about.
one important difference is that 2 rail stock has electrical isolation between the two rails. For 3-rail use this can be ignored, because it’s irrelevant (except that operation of anything powered or triggered by isolated rails, may not operate)
2 rail rolling stock won’t generally cope with tubular track, from what I’ve seen of random pieces I’ve picked up, but copes with modern type track like Fastrack quite easily.
However the couplers don’t match. 2 rail stock generally has Kaydee type couplers which aren’t compatible with 3-rail types.
So if you want to run consists of 2-rail stock on 3-rail nickel-silver, Fastrack or Atlas type track you have the (fairly simple) problem of making “match cars” with the appropriate couplers for the outer ends of the consist.