Abstract Background Platelets are thought to participate in tumor metastasis. However, the relationship between platelet count and prognosis in pancreatic cancer remains unresolved. Methods A chart review of patients undergoing resection for pancreatic adenocarcinoma was undertaken. Demographic, perioperative, and outcome data were collected. Kaplan-Meier survival and Cox regression analyses were used to determine the impact of preoperative platelet count on survival. Results Between June 1995 and March 2003, 109 patients (63% male) with a median age of 68 years (range 42 to 85 years) underwent resection for pancreatic cancer. Univariate analysis demonstrated that platelet count, lymph node or margin status, and histology were associated with survival. In multivariate analysis, the association between increased platelet count and poor survival maintained significance. Conclusions Increased preoperative platelet count is associated with adverse survival outcome in patients undergoing resection for pancreatic cancer. Antiplatelet medications warrant further study in an attempt to improve survival in these patients.