This research was conducted to evaluate the design of hospital ultraviolet germicidal irradiation (UVGI) systems and to assess their effectiveness for inactivating airborne mycobacteria. A computational fluid dynamics (CFD) model was developed and tested by simulating previous experiments measuring the effectiveness of a lab-based UVGI system. Model testing showed reasonable agreement with experimental measurements. The model captured trends similar to the experiments: Effectiveness of an upper-room UVGI system is higher when there is no ventilation compared with when there is ventilation, and wintertime ventilation conditions can markedly decrease the performance of an upper-room UVGI system. The CFD model was then applied to evaluate the design of three hospital patient rooms. A patient and an exam room with upper-room UVGI systems, and a patient room with an exhaust duct system were studied. Results showed that one of the UVGI systems was not very effective, due to the very efficient ventilation design. The other two configurations were reasonably to very effective at inactivating airborne mycobacteria. The most effective application was the one in which the room air-exchange rate was very low. CFD modeling can be useful for assessing whether hospital UVGI installations and ventilation systems are effective for infection control.