BACKGROUND To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. METHODS Some 303 patients were randomized to either short-course RT (5 x 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long-course RT (25 x 2 Gy) and surgery after 4-8 weeks (group 3). RESULTS Demographic data were similar between groups and there were few protocol violations (5.0-6 per cent). Eight patients (2.6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46.6, 40.0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0.164). Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37). CONCLUSIONS Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. BACKGROUND NCT00904813 (http://www.clinicaltrials.gov).