Perioperative serum carbohydrate antigen 19-9 (CA 19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The object of this study was to investigate the predictive factors for survival, including preoperative and postoperative serum CA 19-9 levels in patients with pancreatic cancer. Between 2003 and 2009, a total of 269 patients with pancreatic invasive ductal carcinoma underwent macroscopically curative resection, and pre- and postoperative (within 3 months after surgery) serum CA 19-9 levels were evaluated in all of them. The prognostic significance of clinicopathologic factors was evaluated by univariate and multivariate analyses. Preoperative serum CA 19-9 levels were higher than normal (>37 U/ml, 38-4600 U/ml) in 218 of 269 patients. Of these, after surgery, serum CA 19-9 level returned to within a normal range in 136 patients (62%), whereas 82 patients (38%) remained in the higher-than-normal range. In univariate and multivariate analyses, node metastasis (P < 0.001) and postoperative CA 19-9 level (>37 U/ml) (P < 0.0001) were independent predictors for poor survival. Postoperative CA 19-9 level was higher in patients with microscopically positive surgical margin (P = 0.02). Hepatic recurrence and peritoneal dissemination were associated with postoperative higher CA 19-9 level. Postoperative CA 19-9 level was associated with positive surgical margin and hepatic or peritoneal recurrence and may be a useful predictor for survival in patients with pancreatic cancer.