Background: Pancreatic fistula is a major source of morbidity following distal pancreatectomy. The risk factors for pancreatic fistula are poorly recognized, and the optimal method of stump closure is still controversial. Our aim is to identify risk factors related to pancreatic fistula and to determine the impact of the technique of transection and stump closure on the formation of pancreatic fistula.Methods: An IRB approved retrospective review of 214 consecutive patients who underwent distal pancreatectomy at a single institution from January 1996 to July 2008 was performed. Perioperative and postoperative data were collected and analyzed with particular attention to pancreatic fistula as defined by the International Study Group of Pancreatic Fistula guidelines.Results: The average age was 59 years old; there were more females than males (n=124 vs. n=90). Distal pancreatectomy with splenectomy was performed in 89%. Laparoscopic resection was completed in 13 patients (7%). Pancreatic fistula developed in 30 patients (14%); fistulas were classified as Grade A in 13 patients (45%), Grade B in 15 (52%), and Grade C in 2 patients (7%). The pancreas was transected via stapler in 138 patients, cautery in 68 patients and scalpel in 3 patients (n/a in 5 patients). Of the 138 patients who were transected with stapler, the pancreatic stump was oversewn in 90 patients and not sewn in 47 patients. Pancreatic fistula developed in 11.1% of those remnants which were stapled and oversewn and 12.5% that were stapled alone. Of the 67 pancreatic remnants that were transected with cautery and oversewn, a fistula developed in 4.5% of patients of these patients (p=0.02 compared to stapled and oversewn). In the laparoscopic group (n=13), there was a 38.5% fistula rate. Median length of stay was significantly increased in patients who developed pancreatic fistula compared to those that did not (8.5 days vs. 6 days, p=0.04) Conclusion: The method of transection and management of the pancreatic remnant play a critical role in the formation of pancreatic fistula following distal pancreatectomy. This series suggests that transection using electrocautery followed by oversewing of the pancreatic remnant minimizes the formation of pancreatic fistula. The fistula rate for laparoscopic distal pancreatectomy remains high; this will need to be improved as this technique becomes more prevalent.