This study compared the efficacy and cost of radiation therapy with indomethacin in the prophylaxis of heterotopic ossification following total hip replacement. Twenty-two patients received a radiation dose of 10 Gy in five fractions, 28 patients 8 Gy in one fraction, and 27 patients 25 mg oral indomethacin three times a day for either 7 or 21 days. Patients at higher risk for heterotopic ossification were more likely to receive radiation therapy than indomethacin. At a mean follow-up of 2 years, there were no differences in failure rates between the high-risk patients treated with radiation and the low-risk patients treated with indomethacin. Currently, the patient-billed cost of radiation is $1400 whereas the cost for indomethacin is approximately $100. Indomethacin appears to be as effective as radiation therapy in patients at low to moderate risk for heterotopic ossification and offers significant cost savings.