Background: Splenectomy at the time of resection of esophageal, gastric, or colon cancer has been correlated with inferior longterm survival. No such effect has yet been demonstrated for pancreatic cancer.Study Design: Patients undergoing resection of pancreatic adenocarcinoma with curative intent at Memorial Sloan-Kettering Cancer Center between October 1983 and October 1995 were identified from a prospective clinical database. The impact of splenectomy on hospital stay and survival was calculated with univariate and multivariate nonparametric methods.Results: Of 332 patients undergoing pancreatectomy, 326 with confirmed local or regional disease only formed the study cohort. Of these, 37 underwent concomitant splenectomy (11.4%). Splenectomy was significantly correlated with distal or total pancreatectomy, primary location in tail or body, portal vein invasion or resection, a larger maximal tumor diameter, and an operative blood loss of greater than 2,000 mL. Death or need for reoperation was not affected by splenectomy. Patients undergoing splenectomy had a higher median transfusion requirement (3 versus 1; p = 0.002). The median postoperative length of stay was 15 days regardless of splenectomy. At a median followup of 16.3 months (36.4 months for surviving patients), the median actuarial survival was 12.2 months with splenectomy versus 17.8 months without splenectomy (p < 0.005). On multivariate analysis, splenectomy emerged as an independent factor predictive of decreased postoperative survival (p = 0.02), in addition to pathologic lymph node status (p = 0.0002), tumor diameter (p = 0.0004), and tumor differentiation (p = 0.007). Tumor location within the pancreas and the type of pancreatectomy were not independent prognostic factors influencing survival.Conclusions: After pancreatectomy for pancreatic cancer, splenectomy has no significant measurable impact on postoperative recovery, but has a negative influence on longterm survival independent of disease-related factors. Unless required because of tumor proximity or invasion, splenectomy should be avoided in the operative treatment of exocrine pancreatic cancer at any location.