Radiation therapy is commonly used to prevent heterotopic ossification, and the dose-dependent effects of this treatment have been well documented in patients after total hip arthroplasty (THA). However, the efficacy and dose requirement of radiation therapy to prevent heterotopic ossification of nonsurgical origin have not been studied. The purpose of this retrospective case-control study was to determine the effects of prophylactic radiation therapy on severe heterotopic ossification recurrence, postoperative range of motion (ROM), and wound healing in patients with heterotopic ossification secondary to neurologic deficits. Selection was not blinded, and higher risk patients were generally assigned to the treatment group. Standard doses of radiation therapy did not adequately lower recurrence rates; in fact, there was a higher incidence of heterotopic ossification formation necessitating revision in the treatment group (15.0%) compared to the control group (5.1%). Moreover, patients who received radiation therapy were not more successful at maintaining intraoperative ROM over time. There was a similar incidence of delayed wound healing between groups (12.8% in the control group and 12.5% in the treatment group), and no other negative side effects or complications were observed. These results suggest that the 700 cGy dose of radiation therapy typically used for the prophylaxis of heterotopic ossification associated with THA does not effectively prevent the recurrence of neurogenic heterotopic ossification in high-risk patients. Further studies are needed to determine whether higher doses of radiation therapy will provide more effective prophylaxis for heterotopic ossification.