This study outlines the potential for Computational Fluid Dynamics (CFD) simulation to be used to predict upper-room ultraviolet germicidal irradiation (UVGI) effectiveness to aid system design and the development of future guidance. A numerical study of two wall-mounted UVGI lamps in a mechanically ventilated test chamber is used to assess the influence of modeling parameters on prediction of dose distribution and microorganism inactivation. Irradiance fields for both UVGI fixtures are obtained via radiometry and implemented in the model. A series of sensitivity studies consider the importance of UVGI field accuracy and computational grid and turbulence model selection. Results show that 2D irradiance fields are sufficient for calculating dose and in-activation, whereas a 1D field is inadequate for modeling purposes. Further parametric studies consider the effects of ventilation parameters, UVGI lamp configuration and microorganism susceptibility. These demonstrate the feasibility of modeling the interaction of the airflow and UV field in a room to quantify the dose distribution. Microorganism in-activation can also be accomplished by employing passive scalars and species transport models, however, further validation data are necessary before this can be used to make reliable quantitative predictions.