The antenna pattern should be roughly spherical. So, yes, it should work in a multi-story structure. Mine do – I have three in my two-story (plus basement) home. What is most important is making sure they are placed such that they get a "great" rating in the mesh test. Having the primary (the one connected to the internet via Ethernet) placed in the center with the secondaries one or two rooms away from there (in any direction) is optimal. From there, they will provide coverage to more distant clients (in any direction).