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BACKGROUND: Laparoscopic distal pancreatectomy (LDP) was first reported in 1996. Since then, all publications evaluating LDP have consisted of single center or multi-institutional case series. We hypothesized that a national database inquiry could offer insight into the indications and outcomes of LDP. METHODS: The Nationwide Inpatient Sample was queried for patients undergoing LDP for benign and malignant pancreatic lesions from 1998 to 2009. Univariate and multivariate analyses were performed using logistic regression models, adjusting for age, gender, ethnicity, and comorbidities. RESULTS: 1,908 LDPs were performed between 1998 and 2009. 506 cases were excluded due to unclearly coded ICD-9 diagnoses. The remaining 1,402 LDPs were coded for benign (57.8%) or malignant (42.2%) diseases of the pancreas. The groups were similar for gender, ethnicity, and in-hospital mortality rates but cancer patients were on average 6.9 years older (P=0.0001) and had higher Charlson comorbidity indices (scores ≥ 2: 75.5% vs. 50.8%, P=0.0001). On univariate analyses, patients undergoing LDPs for malignancies had longer lengths of stay (8.95 vs. 6.89 days, P=0.02), higher overall complication rates (34.4% vs. 22.0%, P=0.045), more inadvertent organ injuries (5.5% vs. 1.1%, P=0.03), higher splenectomy rates (93.8% vs. 71.4%, P<0.0001) and increased requirements for blood transfusions (15.8 vs. 6.6%, P=0.019). On multivariate analyses, LDPs performed for cancer were associated with a statistically significant increase in the incidence of splenectomy (OR 5.92, 95% CI 2.32-15.1). In contrast, there were no differences in individual complication rates, including fistulae, infections/abscesses, hemorrhage/hematomas, inadvertent organ injuries, wound complications, organ dysfunction, thromboembolic events, or in-hospital mortality based upon disease indication for LDP. CONCLUSIONS: The reported experiences of single or multiple institutions with LDP for cancerous lesions of the pancreas remain limited. We now report the nationwide experience and outcomes of LDP for patients with benign and malignant pancreatic diseases utilizing a national database. We show that patients undergoing LDP for pancreatic cancer tend to be older, have more comorbities, and are more likely to undergo concurrent splenectomy. However, on multivariate analyses, this does not result in increased in-hospital morbidity or mortality rates. In summary, the application of laparoscopic distal pancreatic resections for malignancies has emerged as a feasible and safe approach with comparable outcomes to resections performed for benign pancreatic lesions. However, long-term oncological outcomes need to be better studied before this technique can be widely accepted as standard of care.