The use of whole pelvic radiotherapy (WPRT) for high-risk and lymph node-positive prostate cancer (PC) remains controversial. The purpose of this study was to evaluate the acute toxicity associated with helical tomotherapy in the treatment of high-risk and lymph node-positive prostate cancer. To do so, twenty-eight patients were treated to a dose of 54 Gy in daily fractions of 1.8 Gy to the pelvic lymph node area, while the prostate and the seminal vesicles received a simultaneous integrated boost (SIB) to a dose of 70.5 Gy. A SIB to a dose of 60 Gy was delivered to the involved lymph node region(s) in 8 patients with pelvic lymph node metastases. All patients received concurrent hormonal treatment. The incidence of grade 2 and 3 acute gastrointestinal (GI) toxicity was 7% and 0% respectively. Grade 2 and 3 acute genito-urinary (GU) side effects were observed in 14% and 4% of the patients respectively. No grade 4 side effects occurred. No increased toxicity was observed in the 8 lymph node-positive patients receiving a simultaneous pelvic nodal dose escalation. In conclusion, WPRT with a SIB to the prostate and seminal vesicles by helical tomotherapy resulted in a favourable toxicity profile. Pelvic nodal dose escalation in node-positive patients is feasible without increasing toxicity.