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Background: Pancreatic fistula continues to be a source of significant morbidity following distal pancreatic resections. The technique of pancreatic division varies widely among surgeons, and there is no evidence that identifies a single method as superior. In our practice, the technique of distal pancreatic resection evolved from cut-and-sew, to stapled technique with green and recently white (vascular) cartridge. The aim of our study was to evaluate the rate of clinically significant fistulas (International Study Group on Pancreatic Fistula (ISGPF) Grade B or C) following distal pancreatectomy, and to identify variables associated with a low rate of fistula development. Methods: Clinical records of all patients who underwent distal pancreatic resections between February 1999 and July 2010 by a single surgeon were retrospectively reviewed focusing on the incidence and type of pancreatic fistula as defined by ISGPF. Study variables included age, gender, surgical approach, extent of resection, ASA classification, type of stapler cartridge, use of Seamguard™, and ISGPF classification. Statistical analysis was performed using Fisher’s exact test, univariate and multivariate logistic regression. Results: Sixty four patients (median age 60, range 21-85; 54 % male) underwent distal pancreatic resection (laparoscopy 50% vs. open 50%). The most common indications were pancreatic adenocarcinoma (N=15; 23%) and neuroendocrine neoplasms (N=14; 22%). Clinically significant pancreatic fistula developed in 23% (N=15). The rate of fistula with cut-and-sew technique was 36% (4/11), with stapled green cartridge 31% (9/29) and only 5% (1/21) with stapled vascular cartridge. Univariate logistic regression identified vascular cartridge size (p=0.04, OR 0.11) and open stapled technique (p=0.05, OR 0.12) as variables significantly associated with a low fistula rate. Both vascular cartridge size (p=0.05, OR 0.10) and open stapled technique (p=0.04, OR 0.08) remained significant when analyzed by multivariate logistic regression. Division of pancreatic parenchyma with vascular cartridges resulted in significantly (p=0.03, OR 9.0) lower fistula rate compared to green cartridges. The use of Seamguard™ did not affect fistula rate (16% vs. 27%; p=0.34), nor did the performance of multi-visceral resection vs. distal pancreatectomy/splenectomy alone (21% vs. 23%, p=1.0). Conclusion: The optimal technique of pancreatic division has not been conclusively established. Dividing the pancreas utilizing vascular (2.5mm) staple cartridge significantly decreased the rate of clinically significant pancreatic fistula, and we continue to favor this technique in our practice. A prospective randomized trial is necessary to validate these results.