A numerical simulation of aerodynamic interaction was conducted on a multi-rotor aircraft. The objective was to determine the aerodynamic interaction effects with and without fuselage. For this purpose, time-accurate unsteady flow calculations were made by a three-dimensional unstructured mesh CFD flow solver. As an application of the present method, simulations were conducted for a quad-rotor UAV. Without a fuselage, the tip vortices from the upstream rotors directly affect downstream rotors, thus thrust variations of rear rotors are increased. With fuselage, as the direction and strength of vortices generated by upstream rotors are changed, the pitching and rolling moments of a vehicle are decreased. It was found that the aerodynamic interaction between not only rotors and but also rotor-fuselage should be considered seriously for determining multi-rotor flight.