The effectiveness of UV-C irradiation at inactivating airborne pathogens is well proven, and the technology is alreadyadvocated for control of some respiratory diseases such as Tuberculosis. UV-C air disinfection is also commonly promotedas an energy efficient way of reducing infection risk in comparison to increasing ventilation. However determining howand where to apply UVGI devices for the greatest benefit is still poorly understood. This paper focuses on upper-roomUVGI systems, where microorganism inactivation is accomplished by passing contaminated room air through an openUV field above the heads of occupants. Multi-zone models are developed to assess the potential impact of a UVGIinstallation across a series of inter-connected spaces such as a hospital ward; this may comprise rooms for one or morepatients that are all connected to a common zone that may be a corridor or may act as a communal space, housing forexample the nurses station. Simulation of dose couples the ventilation, air mixing and upper-zone average field to explorefactors influencing device coverage. A first-order decay model of UV inactivation is coupled with the room air model tosimulate patient room and whole-ward level disinfection under different mixing and UV field conditions. Steady-statecomputation of quanta concentrations are applied to the Wells-Riley equation to predict likely infection rates. Simulationof a hypothetical ward demonstrates the relative benefits of different system options for susceptible patients co-located withan infectious source or in nearby rooms. In each case energy requirements are also calculated and compared to achievingthe same level of risk through improved ventilation. A design of experiment technique is applied to sample the design spaceand explore the most effective system design for a given scenario. Devices are seen to be most effective where they arelocated close to the infectious source. However, results show that when the location of the infectious source is not known,locating devices in patient rooms is likely to be more effective than installing them in connecting corridor or communalzones.