BACKGROUND AND PURPOSE: To determine the effect of organ motion and set-up uncertainties on IMRT dose distributions for prostate. METHODS: For five patients, IMRT techniques were designed to irradiate the CTV (prostate plus seminal vesicles). Technique I delivered 78 Gy to PTV1 (CTV+10 mm margin). Technique II delivered 68 Gy to PTV1, and a 10 Gy boost to PTV2 (CTV+an anisotropic margin of 0 to 5 mm). Technique III delivered 68 Gy to PTV1 and simultaneously 78 Gy to PTV2. Uncertainties were simulated using population statistics of organ motion and set-up accuracy. The average TCP (TCPpop) of the CTV and average NTCP (NTCPpop) of the rectal wall were calculated. RESULTS: The planning TCP was a good predictor for TCPpop for Techniques I and II. Technique III was sensitive for geometrical uncertainties, reducing TCPpop by 0.8 to 2.4% compared to planning. NTCPpop was reduced for Technique III by a factor 2.6 compared to Technique I. For all plans, the planning NTCP was strongly correlated with NTCPpop. CONCLUSIONS: Dose distributions created with Techniques I and II are insensitive for geometrical uncertainties, while Technique III resulted in a reduction of TCPpop. This reduction can be compensated by a small dose escalation, while still resulting in an NTCPpop of the rectal wall that is lower or comparable to Technique I.