I am using Matx board in Mid size tower. Board is Maximus V in Cooler Masater mid case. No issue at all there is enough room to put two PCIE 3.0 cards. But i always use one power full card so no prob. If any thing i get better cooling then my previous ATX board.
Just be careful choosing Cpu cooler. Some cooler tend to take alot of room, and might hinder one ram slot. Easily fixed if your cooler fan move up and down.