Objective: This study reviewed pancreaticoduodenectomy (PD) for pancreatic cancer. Methods: We reviewed 1382 patients who underwent a PD for pancreatic cancer between April 1970 and November 2005. Results: A total of 1382 PDs were performed for pancreatic cancer, with 600 PDs performed in the last five years. Pathologic diagnoses included 1168 ductal adenocarcinomas, 93 malignant neuroendocrine tumors, 90 IPMNs with invasive cancer, and 31 other neoplasms. Patients with ductal adenocarcinoma were analyzed in detail: the most common preoperative symptoms included jaundice (75%), weight loss (51%), and abdominal pain (38%). Seventy-two percent of the PDs were pylorus preserving and 6% were total pancreatectomies. The median tumor diameter was 3 cm, 43% of the resections had positive margins, 78% had positive nodes, 52% had small vessel invasion, and 91% had perineural invasion. The perioperative morbidity was 38%, with the most common complications being delayed gastric emptying (14.2%), wound infection (8.6%), and pancreatic fistula (4.7%). Median postoperative stay was 9 days. The perioperative mortality, by decade, was 30.4% in the 1970s (p<0.001 compared to the 2000s), 4.5% in the 1980s (p=0.03), 1.9% in the 1990s, and 1.1% in the 2000s. The median survival for all patients with ductal adenocarcinoma was 17 months (1-year survival=65%, 5-year survival=17%). The median survival with no positive lymph nodes, negative margins, and tumor diameter less than 3 cm was 32 months (1-year survival= 78%, 5-year survival=38%). In a cox proportional hazards model, pathologic factors that had a significant negative impact on survival included margin status (hazard ratio, HR=1.6), lymph node status (HR=1.4), and tumor diameter (HR=1.4). Conclusion: This is the largest single institution experience with resected pancreatic cancer. Patients who have cancers with favorable pathological features have a significantly improved long-term survival.