There's no difference in compiling to ES5 versus hooking into the module loading mechanism to compile on the fly, in terms of the end-result. The only practical difference is that precompiling means your modules will load faster the first time, but there will be no difference for subsequent loads since modules are cached. I'm guessing the caveat for running something like babel-register in production is the first-load performance penalty, as well as having less control over the compilation process. However, if you are ok with configuring babel through .babelrc files alone, and you're ok with the first-load performance penalty, I don't see what it'd be any worse than precompiling to ES5. (There may be subtle differences in debugging due to the lack of source maps, but I don't know enough to comment on that with any degree of certainty.)