OBJECTIVE: Prostate cancer represents the second most common malignancy in the world and majority of patients have diagnosis of localized disease. The aim of the present study was to compare two cohorts of patients treated with moderate hypofractionation (MHRT) or stereotactic body radiation therapy (SBRT). METHODS: We included patients treated between 2010 and 2015. Inclusion criteria were: adenocarcinoma of the prostate; class risks low or intermediate; WHO performance status 0-2. We evaluated rectal, gastrointestinal toxicity and genitourinary. Measures of outcome were biochemical disease-free survival and overall survival. Propensity score was used to approximate the balance in covariates. RESULTS: 209 patients were included, treated with MHRT (n = 109) or SBRT (n = 100). Median follow-up time was 37.4 months. Rates of biochemical disease-free survival at 1- and 3 years were 100 and 95%, respectively. There was no significant difference between the two groups (p = 0.868). Rates of overall survival at 1- and 3 years were 100 and 97.1%, respectively with no differences between the two groups (p = 0.312). After propensity scoring matching, no differences were observed in terms of acute and late rectal and gastrointestinal toxicity. While mild genitourinary side-effects were more common in SBRT group (45.5% vs 19.5 %), Grade 2 and 3 toxicity was increased after MHRT (11.7% vs 2.6 %; p = 0.029). CONCLUSIONS: Moderate hypofractionation and SBRT are two effective and safe options for the treatment of low- and intermediate-risk prostate cancer. The analysis showed no difference in terms of disease's control and survival but increased moderate and severe toxicity after MHRT. ADVANCES IN KNOWLEDGE: Moderate hypofractionation and SBRT are comparable in terms of efficacy while moderate and severe toxicity is more common in the first one.