A Phase I/II study was initiated to evaluate complications of Orthovoltage intraoperative radiation therapy utilized in the treatment of patients with incompletely resected recurrent gynecologic malignancies. There were no osseous, vascular, neurologic, or ureteral complications. Of the 23 treated patients, 2 patients (8.7%) had complications outside the treated area. Survival of patients treated with intraoperative radiation therapy was highest among patients treated to a field of ≤ 3 cm in greatest diameter and a tumor thickness of ≤1 mm. A subgroup of patients (5) with microscopically positive margins following total pelvic exenteration demonstrated an absence of recurrence in the treated field. The role of intraoperative radiation therapy (IORT) in the treatment of recurrent and incompletely resectable gynecologic malignancies remains investigational.