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Background: The most common complication after distal pancreatectomy (DP) is leakage from the pancreatic stump closure. Clues to the leakage may help in prevention.Objective: We sought to determine the incidence, severity and risk factors for leakage using a large number of DP cases performed with traditional open surgery. Patients and Methods: Our prospectively maintained single-surgeon database identified 223 consecutive DPs between 1992 and 2008. The operation was the same in all cases performed with a hand-sewn fish-mouth closure of the pancreatic stump. Using daily drain amylase measurements stump leakage (LEAK) was defined and graded as no LEAK, Grade A, B, or C according to the severity classification system of the International Study Group on Pancreatic Surgery (ISGPS). “Clinically relevant” LEAK was defined as ISGPS Grade B/C (LEAK) leaving the no LEAK and Grade A cases in a “Non-clinically relevant” group (No LEAK). A public web-based calculator was used to standardize the ISGPS system. The incidence of LEAK and risk factors for clinically-relevant LEAK were assessed. Results: ISGPS grading of these 223 cases were: No LEAK 53%, Grade A 32%, Grade B 13.9%, and Grade C 0.9% with an overall mortality of zero. Therefore the clinical-relevant LEAK rate was 14.8% (Grade B+C). Of these B/C cases 24% were due to surgical drain failure - lack of patency and/or misplaced from their original location. The following risk factors were significant by univariate analysis: obesity (BMI>30) in 52% of LEAK cases vs. 21% of No LEAK cases, neuroendocrine tumors (NET) in 30% of B/C cases vs. 10% of No LEAK cases, soft pancreatic texture (88% of LEAK vs. 66% of No LEAK cases), and blood loss > 1000ml (21% of LEAK cases vs. 7% of No LEAK cases). In 46 cases with preoperative endoscopic ablation or stenting of the major pancreatic sphincter a significant decrease in the incidence of ablation/stenting was observed in the LEAK cases (3%) vs. No LEAK cases (24%). Multivariate analysis identified the following to be significantly associated with LEAK: BMI > 30 (odds ratio [OR], 3.04), soft pancreatic texture (OR, 4.89), intraoperative blood loss > 1000 ml (OR, 7.01), and those who did not undergo preoperative major pancreatic sphincter ablation/stenting (OR, 9.51). Conclusions: Clinically-relevant LEAK was observed after DP in 14.8% of the 223 cases, one quarter of these B/C cases might have been just non-relevant leaks (Grade A) if the drain had not malfunctioned. The risk for a clinically relevant LEAK after DP was associated with factors that retard healing and with an intact major pancreatic sphincter. The latter suggests that LEAK may be due to the many causes of sphincter spasm that might promote leakage from pancreatic stump due to back pressure.