Abstract: Pancreatic cancer is a highly aggressive disease with poor survival. The only effective therapy offering long-term survival is complete surgical resection. In the setting of nonmetastatic disease, locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins. Few studies have evaluated the implications of the latter in depth. The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome. By retrospective analysis of prospectively maintained data from 360 patients operated for pancreatic cancer at our institution, we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures. At the same time, perioperative severe morbidity and mortality are not significantly increased. Our observations suggest that pancreatic cancer should be resected whenever technically feasible, including, cases of locally advanced disease