PURPOSE: The purpose of this study is to demonstrate quantitatively the complementary relationship between the introduction of intensity modulated radiation therapy (IMRT) and planning target volume (PTV) margin reduction with an image guided technique in reducing the risk of rectal toxicity in dose-escalating prostate radiation therapy. METHODS AND MATERIALS: Three-dimensional conformal radiation therapy (CRT) and IMRT plans were generated for 10 patients with prostate cancer based on 2 PTV margin protocols (10/8 mm and 6/5 mm) and 2 dose prescriptions (70 Gy and 78 Gy). The normal tissue complication probability (NTCP) for each of the 8 scenarios was calculated using the Lyman-Kutcher-Burman model to estimate the risk of rectal and bladder late toxicity. The conformity and homogeneity indices of PTVs were calculated for each plan. RESULTS: The IMRT plans showed superiority in conformity and inferiority in homogeneity over 3-dimensional CRT plans. The rectal NTCPs were increased 3.5 to 4.1 times when the prescribed total dose was changed from 70 Gy to 78 Gy and the dose delivery and the image guided radiation therapy techniques remained unchanged. PTV margin reduction was shown to reduce the value of rectal NTCP significantly. Overall, implementing the IMRT technique alone could reduce the NTCP values only by 2.1% to 7.3% from those of 3-dimensional CRT. The introduction of both IMRT and PTV margin reduction was found to be necessary for rectal NTCP to remain <5% in the dose escalation from 70 to 78 Gy. CONCLUSIONS: The complementary relationship between the introduction of IMRT and PTV margin reduction was proven. We found that both approaches need to be implemented to safely deliver a curative dose in dose-escalating prostate radiation therapy.