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ABSTRACT: The International Study Group of Pancreatic Fistula (ISGPF) classification allows comparison of incidence and severity of postoperative pancreatic fistula (POPF). Its post hoc character, however, does not provide a guideline for the treatment of POPF in individual patient. We therefore studied the association of POPF type A-C on secondary surgical morbidity and mortality in patients undergoing pancreatic resection. Between 3/2001-12/2007, 483 patients underwent pancreatic resections. POPF were classified according to the ISGPF classification. All patient data were entered in a clinical data management system prospectively. Patients who developed POPF had significantly more vascular but not other surgical complications than patients without POPF. Patients with POPF A had no vascular or surgical complications. Twenty one of the 29 patients with POPF C had surgical complications (17 vascular complications). Mortality attributed to surgical complications after POPF C was 5/29. A soft pancreatic consistency (OR 8.5; p < 0.008) and a high drain lipase activity on postoperative day 3 (OR 4.4; p = 0,065) were predictors for the development of POPF C. POPF C is associated with vascular complications like erosion bleeding and other surgical complications like delayed gastric emptying or pleural effusions. A soft pancreatic consistency and a high drain lipase activity on postoperative day 3 are early predictors for the development of POPF C.