In recent years, many efforts have focused on combined radiotherapy and chemotherapy as adjuvants to curative surgery in patients with stage II and III (UICC) rectal carcinomas. Intraoperative radiotherapy (IORT) makes it possible to increase the total irradiation dose in a locally restricted area while sparing normal mobile organs, but it is limited by increased late toxicity. A prospective phase I/II study was designed to evaluate the efficacy of moderate-dose intraoperative and external beam radiotherapy (IO-EBRT), in some cases with concomitant chemotherapy. Sixty-three patients with a stage II or III rectal carcinoma were eligible for analysis (median follow-up 30.6 months). Fifty-four patients had undergone a complete resection (RO). Mean IORT dose was 11.3 Gy and mean EBRT dose 41.4 Gy. In 45 patients (71.4%) concomitant chemotherapy was delivered (5-FU, leucovorin). Two patients suffered local failure. However, overall local tumor control was markedly improved compared to historical controls (96.8% vs 66.2%). Patients treated with IO-EBRT showed a reduced incidence of distant metastases after concomitant chemotherapy (17.6% vs 38.8%). A 4-year actuarial relapse-free survival of 82% was obtained after IO-EBRT plus chemotherapy, and 59% after IO-EBRT alone. The postoperative course was unremarkable in 47.6% of patients. No radiation colitis or neuropathy occurred. Moderate-dose IORT and EBRT is safe, taking into account related late toxicities. It is an effective local treatment approach, resulting in an encouraging local control rate.