First of all, microtype will never issue an error message when it encounters a font that it doesn't know about, so it is always "compatible" in your sense.
With regards to "effective": For protrusion of unknown fonts (Calibri being one of them), microtype will use fallback settings and write an info about this in the log file. These fallback settings (in microtype.cfg) are quite conservative and contain protrusion settings only for the characters which are most likely to require protrusion (but this is still more than what the settings from luaotfload contain, which actually only protrude the punctuation characters). This should give reasonable results in most cases. Of course, it is possible, and probably preferable, to create a proper configuration file for the font in question, but this requires some time and a good eye.
With expansion the situation is even better, as it doesn't require dedicated font settings, and will just work, even for unknown fonts.
XeTeXnorLuaTeX(orCalibriinTeX, for that matter) and have only usedmicrotypewithpdflatex(withComputer Modern). – nutty about natty Jun 28 '13 at 14:42microtype: that it just looks a lot better! – nutty about natty Jun 28 '13 at 14:44.cfgfile is supplied, and yes,microtypestill produces more pleasing output. And you can write your own configuration file if you have the patience. – Thérèse Jun 29 '13 at 17:35microtype&Calibriwill just look smashing by default -- even without taking a look beneath the bonnet... – nutty about natty Jun 29 '13 at 18:27microtypemanual. Use the files in/texlive/2013/texmf-dist/tex/latex/microtype(or wherever they dwell on your system) as models. Nothing needed except — hah! — a very good eye, time, and abundant patience. – Thérèse Jun 29 '13 at 20:24