We report a prospective, randomised, blinded clinical comparison of the use of indomethacin or radiation therapy for the prevention of heterotopic ossification (HO) in 75 adults who had open reduction and internal fixation of acetabular fractures through either a Kocher-Langenbeck, a combined ilioinguinal and Kocher-Langenbeck, or an extended iliofemoral approach. Indomethacin, 25 mg, was given three times daily for six weeks. Radiation with 800 cGy was delivered within three days of operation. Plain radiographs were reviewed and given Brooker classification scores by three independent observers who were unaware of the method of prophylaxis. One patient died from unrelated causes and two were lost to follow-up, leaving 72, 33 in the radiation group and 39 in the indomethacin group, available for evaluation at a mean of 12 months (6 to 48). There was no significant difference in the two groups in terms of age, gender, injury severity score, estimated blood loss, delay to surgery, head injury, presence of femoral head dislocation, or operating time, and no complications due to either method of treatment. The final extent of HO was already present by six weeks in all patients who were followed up. Three patients in the radiation group and five who received indomethacin developed HO of Brooker grade III. Two patients in the indomethacin group developed Brooker IV changes; both had failed to receive proper doses of the drug. Cochran-Armitage analysis showed no significant difference between the two treatment groups as regards the formation of HO. Indomethacin and single-dose radiation therapy are both safe and effective for the prevention of HO after operation for acetabular fractures. Radiation therapy is, however, approximately 200 times more expensive than indomethacin therapy at our institution and has other risks.