Purpose: This is a mono-institutional study of acute and late toxicities and early biochemical control of a retrospective series of 75 prostate cancer patients treated with moderate postoperative hypofractionation delivered by helical tomotherapy (HT).Patients and methods: From April 2013 to June 2017, 75 patients received adjuvant (n=37) or salvage (n=38) treatment, delivering to prostate bed a total dose of 63.8 Gy (equivalent dose in 2-Gy fraction..67.4 Gy) using 2.2 Gy fractions. Whole-pelvis irradiation was performed in 63% of cases (median dose, 49.3 Gy; range, 48-55.1 Gy). Concurrent hormonal therapy was administered in 46% of cases. Common Terminology Criteria for Adverse Events (version 4.0) was adopted for acute and late genitourinary (GU) and gastrointestinal (GI) toxicity evaluations. Biochemical progression was defined as PSA level increase of >= 0.2 or more above the postoperative radiotherapy (RT) nadir.Results: Acute GU toxicities were as follows: G1 in 46% and G2 in 4%, detecting no G >= 3 events. For GI toxicity, we recorded G1 in 36% and G2 in 18%. With a median follow-up of 30 months (range, 12-58 months), we found late toxicity G2 GI in 6.6% and G >= 2 GU in 5.3%, including two patients who underwent surgical incontinence correction. Acute toxicity and diabetes were found to be predictive of late GI >= 2 toxicity (P=0.04 and P=0.0019). Actuarial 2- and 3-year biochemical recurrence-free survivals were 88% and 73%, respectively, for the entire population.Conclusion: In our experience, moderate hypofractionated postoperative RT with HT was feasible and safe, with reports of low incidence of toxicity and promising biochemical control rates.