XS is the way you hooked from Perl to C from the beginning. Inline::C is a relatively new way to wrap around XS - it actually generates, then compiles the appropriate XS file(s).

I would feel more comfortable if my tools used hand-rolled XS as opposed to Inline::C. However, that's a preference with nothing to back it. Of course, Inline::C is an Ingy-module. I've never broken an Ingy-module. They are way cool ... sometimes too cool - kinda like Damian-code. You'll never understand it and it should never break. But, if it does ... you're screwed.

Now, Inline::C can do some really neat things, like compile C expressions at runtime, kinda like an eval for C. There's penalties, but I don't think they're insurmountable.