Background: As an alternative to dose-escalated conventionally fractionated radiotherapy, hypofractionation capitalizes on the unique radiobiology of prostate cancer cells. This study reports the long-term clinical outcomes and late treatment-related toxicities in patients with clinically localized prostate adenocarcinoma treated with hypofractionated radiation therapy at a single tertiary-care institution. Methods: Between 1996 and 2008, 822 patients were treated with hypofractionated intensity modulated radiation therapy (IMRT) (70 Gy in 2.5 Gy/fraction) directed to the prostate gland with or without coverage of the seminal vesicles over a 5.5 week period. Actuarial rates of biochemical relapse free survival by the nadir + 2 definition (bRFS), distant metastasis free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes were available and measured according to the National Cancer Institute Common Toxicity Criteria (v3) in 773 (94%) of the patients. Results: The median follow-up was 8.5 years (range: 0-14.2 years). The overall 10-year bRFS, DMFS, and OS rates were 69.6%, 86.4%, and 71.7%, respectively. By National Comprehensive Cancer Network (NCCN) low-, intermediate-, and high-risk groups, the 10-year bRFS rates were 86.9%, 74.1%, and 41.3%, respectively. The rate of grade 2 or worse late genitourinary (GU) and gastrointestinal (GI) toxicity rates were 17.2% and 5.6 %. Only 1.4% of patients experienced late equal to or greater than grade 3 GU toxicity and 1.0% experienced late greater than or equal to grade 3 GI toxicity. Of those who had any toxicity during the follow-up period, 47% and 65% of patients experienced resolution or improvement in their GU and GI symptoms, respectively. Conclusions: Hypofractionated IMRT for localized prostate cancer provides excellent long-term relapse-free survival rates that are comparable to historical studies using conventional fractionation. With modern IMRT and image guidance, HFRT has an acceptably low incidence of late GU and GI toxicities, and appears to be a suitable treatment alternative to conventional fractionation.