85 Background: To assess the biochemical control rates and long-term rectal side effect profile of hypofractionated image guided radiation therapy for prostate cancer. We hypothesize that daily CT-based image guidance will allow a higher dose per fraction to be safely administered, shortening the overall treatment time from 8 weeks to 4-5.5 weeks. METHODS: 160 patients were treated with image guided radiation therapy with or without adjuvant hormonal ablation between 2005 and 2009 for patients <= T3a N0 M0. Patients were classified into risk groups with 51 patients defined as low risk, 67 as intermediate risk, and 43 as high risk. Mean age was 70.2 years. All patients were treated with 60/67.6/70/70.2 Gy to the prostate divided into 20/26/28/27 fractions. 57% of patients received hormone therapy. Daily CT or fiducial-based image guidance was performed prior to each fraction. The median follow up was 34 months. Biochemical control was defined by the Phoenix definition. Rectal toxicity was graded by the CTCAE 4.0 scale. In general patients with rectal bleeding more than once per week were started on rectal steroids. RESULTS: 12/160 (7.5%) of patients had late grade 2 or worse rectal toxicity after radiation treatment. The Kaplan-Meier estimate for grade 2 rectal toxicity at 2 years was 6.9%. The crude rate of biochemical no evidence of disease was 96.3%. Kaplan Meier estimates for biochemical no evidence of disease at 3 and 5 years are 0.98/0.84, 0.97/0.97, and 1.0/0.67 for low, medium, and high-risk patients respectively. Log-rank analysis showed no statistically significant difference among the dosing regimens for toxicity-free survival (p=0.24). CONCLUSIONS: With daily image guidance hypofractionated radiation therapy is clinically safe with moderate late rectal toxicity. Early follow-up suggests high efficacy. Ongoing and future randomized trials such as RTOG 0415 will be required to confirm these findings. No significant financial relationships to disclose.