Local recurrence affects approximately 50% of patients undergoing surgery for pancreatic adenocarcinoma. To lower the incidence of locoregional recurrence, the combination with surgery of adjuvant radiotherapy has been proposed. The latter is based on external radiotherapy (ERT), intraoperative radiotherapy (IORT) or their combination. To evaluate the impact on local control and survival, results achieved in a a group of patients undergoing surgical resection and combined adjuvant radiotherapy, are analyzed. 17 patients with adenocarcinoma of the exocrine pancreas were treated with a therapeutic protocol based on pancreatectomy and intraoperative radiotherapy (IORT) to the tumor bed (10 Gy) followed by postoperative radiotherapy (50 Gy); 9 patients underwent also preoperative radiotherapy (5 Gy) to the pancreas and liver. With a median follow-up of 45 months, in 3 patients (17.6%) local recurrence was observed while 12 patients (70.6%) showed liver metastases or peritoneal spread. Median survival was 17.5 months and actuarial survival at 2 and 5 years was 41.2% and 11.2%, respectively. As compared to a moderate local control, the prognosis of patients undergoing surgical resection remained disappointing. Thus, the effort of improving results with new therapeutic modalities as preoperative radiochemotherapy and adjuvant chemotherapy, seems justified.