One standing problem in the therapy for pancreatic cancer is peritoneal recurrence after pancreatectomy. We have established EIPL (extensive intra-operative peritoneal lavage) therapy as a very simple and non-aggressive prophylactic treatment for peritoneal dissemination of gastric cancer patients with peritoneal free cancer cells. In this study, the impact of EIPL therapy in preventing peritoneal recurrence in patients with pancreatic cancer after a curative surgical operation is analyzed. This study was based on 39 consecutive patients with invasive ductal adenocarcinoma of the pancreas who underwent curative surgical treatment. The patients were divided into two groups: the non-EIPL group, patients without EIPL therapy (from 1995 to 2000) (n=24); and the EIPL group, patients with EIPL therapy (from 2001 to 2003) (n=15). Clinicopathological findings, recurrence patterns and cancer-free survival were compared between the two groups. In addition, to identify free cancer cells during the operation, both carcinoembryonic antigen (CEA)- and cytokeratin 20 (CK20)-specific intraoperative real-time RT-PCR was performed immediately after laparotomy, lymph node dissection and removal of the pancreas in six patients with curative pancreatic cancer. Peritoneal, hepatic, lymphatic, local, and extra-abdominal recurrence rates in the EIPL and non-EIPL groups were 6.7, 40.0, 26.7, 13.3 and 13.3%, and 45.8, 50.0, 20.8, 29.2 and 20.8%, respectively. Among these recurrence patterns, the peritoneal recurrence rate of the EIPL group was significantly lower than that of the non-EIPL (P=0.013). Real-time RT-PCR analysis identified intra-peritoneal free cancer cells in 0, 33 and 67% of patients immediately after laparotomy, lymph node dissection and removal of the pancreatic cancer, respectively. After EIPL therapy, however, no cancer cell was detected in the peritoneal cavity. EIPL therapy was the independent negative risk factor for peritoneal recurrence (P=0.044), and the cancer-free 2-year survival of the EIPL group showed improvement compared with that of the non-EIPL group and was near statistical significance (P=0.097). EIPL therapy significantly prevented peritoneal recurrence after curative operation of pancreatic cancer, and it may contribute to reducing the mortality rate of this aggressive disease. Continued investigation of this promising treatment regimen is warranted.