OBJECTIVES: Hypofractionated radiotherapy (HypoRT) uses larger daily fractions and shortens the overall treatment time compared to conventionally fractionated radiotherapy (ConvRT).  This can improve therapeutic outcomes in prostate cancer and reduce the costs associated with radiotherapy.  The objective is to evaluate clinical outcomes and perform an economic evaluation of HypoRT versus ConvRT regimens.  METHODS: The cohort consists of low- and intermediate-risk prostate cancer patients treated at the McGill University Health Center Radiation Oncology Department from Nov. 2002 to Jul. 2013.  Biochemical failure was the main clinical outcome and defined as the nadir PSA level plus 2ng/ml. Kaplan-Meier analyses were performed to evaluate the time to clinical outcomes. Cox proportional hazards model was used to evaluate the association between the clinical outcomes of HypoRT versus ConvRT, adjusted for covariables.  RESULTS: With a median follow-up of 90 months, the 8- year biochemical relapse-free survival rates were 93% for low risk patients treated with the HypoRT regimen, compared to 82% among intermediate risk patients receiving the HypoRT regimen, and to 67% for intermediate risk patients in the ConvRT group. A significant association was found between type of regimen and biochemical failure (HR_Hypo/Conv = 0.495; 95% CI 0.256-0.996). In addition, the cost estimates for the HypoRT regimen ranged from $5,718.80 to $6,254.00; compared to ConvRT, which ranged from $8,802.70 to $9,614.40. CONCLUSIONS: This study highlights the potential therapeutic gains and cost savings of using a HypoRT regimen in patients with low and intermediate risk prostate cancer, versus ConvRT.