A prospectively randomized controlled clinical trial was performed comparing surgical resection and intraoperative radiotherapy (IORT) with conventional therapy in adenocarcinoma of the stomach. Patients in the experimental group underwent gastrectomy, and IORT was administered to their gastric bed (20 Gy using 11 to 15 MeV electrons). Patients in the control group underwent gastrectomy alone for early-stage lesions confined to the stomach (stages I to II) or resection and postoperative external beam radiotherapy to the upper abdomen (50 Gy using 6 to 10 mV photons) for advanced-stage lesions extending beyond the gastric wall (stages III to IV). One hundred patients were screened for the study, of whom 60 were randomized and underwent exploratory surgery. Nineteen patients were excluded intraoperatively because of unresectability or metastatic disease, leaving 41 patients in the study. Seven patients (17%) died of complications. The median survival for patients with tumors of all stages was 25 months for the IORT group and 21 months for the control group (p = 0.99). Locoregional disease failures occurred in 7 of 16 (44%) IORT patients and in 23 of 25 (92%) control patients (p < 0.001). Complication rates were similar between IORT and control patients. Although IORT failed to afford a significant advantage over conventional therapy in overall survival, IORT did significantly improve control of locoregional disease.