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To analyze in-hospital mortality after pancreatectomy using a large national database.Pancreatic resections, including pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy, remain the only potentially curative interventions for pancreatic cancer. The goal of this study was to define factors affecting outcomes after pancreatectomy for neoplasm.A retrospective analysis was performed using all patients undergoing pancreatic resections for neoplastic disease identified from the Nationwide Inpatient Sample from 1998 to 2003. Crude in-hospital mortality was analyzed by χ2. A multivariable model was constructed to adjust for age, sex, hospital teaching status, hospital surgical volume, year of resection, payer status, and selected comorbid conditions.In all, 279,445 patient discharges were identified with a primary diagnosis of pancreatic neoplasm. A total of 39,463 (14%) patients underwent resection during that hospitalization. In-hospital mortality was 5.9% with a significant decrease from 7.8% to 4.6% from 1998 to 2003 by trend analysis (P < 0.0001). Resections done at low (<5 procedures/year)- and medium (5–18/year)-volume centers had higher mortality compared with those at high (>18/year)-volume centers (low-volume odds ratio = 3.3; 95% confidence interval, 2.3–4.; medium-volume, odds ratio = 2.1; 95% confidence interval, 1.5–3.0). The proportion of procedures performed at high volume centers increased from 30% to 39% over the 6-year time period (P < 0.0001) by trend test.This large observational study demonstrates an improvement in operative mortality for patients undergoing pancreatectomy for neoplastic disease from 1998 to 2003. In addition, a greater proportion of pancreatectomies were performed at high-volume centers in 2003. The regionalization of pancreatic surgery may have partially contributed to the observed decrease in mortality rates.