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Background Laparoscopic distal pancreatectomy is being performed more frequently for benign and low-grade malignant neoplasms of the body and tail of the pancreas. Data continues to emerge comparing outcomes of laparoscopic and open distal pancreatectomy. Objective The aim of this study was to investigate short-term outcomes after laparoscopic distal pancreatic resection compared to open distal pancreatic resection at a single, high-volume institution. Methods We reviewed the medical records of all patients who underwent distal pancreatic resection since March 1991. We compared demographic and perioperative data between patients who underwent laparoscopic versus open distal pancreatectomy from January 2001 to June 2009. For the purposes of analysis, the laparoscopic converted to open cases were included in the open group. Continuous variables were compared using Student’s t-test or Wilcoxon rank-sum test. Categorical variables were compared using chi-square or Fisher’s exact tests. Results A total of 332 patients underwent distal pancreatectomy over an 18-year period. Beginning in 2001, 86 (29.3%) were attempted and 65 were completed laparoscopically with a conversion rate of 24.4%. Reasons for conversion included hemorrhage (8), inflammatory or invasive lesion (6), difficult dissection (6), and injury to colon (1). Eleven patients (52.4%) in the converted group had adenocarcinoma on final pathology. In comparison to open distal pancreatectomy performed since 2001 (n=208), laparoscopic pancreatectomy was statistically similar with respect to patient demographics, operative times, and rates of splenic preservation, positive margins, pancreatic fistula, reoperation, and mortality. The laparoscopic approach was less likely to be used for pancreatic ductal adenocarcinoma (5% vs. 29.8%, p<0.0001). Laparoscopic distal pancreatectomy patients had lower median blood loss (150 vs. 1000 ml, p<0.0001), smaller median tumor size (1.2 vs. 4 cm, p<0.0001), and shorter average length of resected pancreas (7.6 vs. 9.8 cm, p<0.0001). Those in the laparoscopic group had fewer overall (29% vs. 44.2%, p<0.05) and major (10.8% vs. 22.6%, p<0.05) complication rates as well as shorter postoperative hospital stays (median 5 vs. 6 days, p<0.0001).Conclusions Laparoscopic pancreatic resection can be performed safely and effectively in patients with small, benign or low-grade malignant neoplasms of the body and tail. When feasible in selected patients, the laparoscopic approach offers fewer complications and shorter postoperative hospital stays.