Identification of prognostic markers is important to establish a perioperative therapeutic strategy for resectable cholangiocarcinoma (CC). The aim of this study was to investigate whether perioperative serum carbohydrate antigen 19-9 (CA19-9) levels can predict survival of patients who underwent surgical resection for CC. The study included 106 patients who underwent surgical resection for CC. Serum CA19-9 levels were measured preoperatively after biliary drainage and postoperatively about 4 weeks after surgery. The association of clinicopathological factors (including perioperative serum CA19-9 levels) with overall survival (OS) was analyzed with univariate and multivariate analyses. Differences in OS were significant between groups divided on the basis of two preoperative CA19-9 cutoff values (in U/ml) of 37 and 200 and three postoperative CA19-9 cutoff values (in U/ml) of 37, 100, and 200. In multivariate analysis, absence of postoperative adjuvant chemotherapy (P = 0.002), lymph node metastasis (P = 0.0002), preoperative CA19-9 (≥ 200 IU/ml) (P = 0.03), and postoperative CA19-9 (≥ 37 IU/ml) (P < 0.0001) were identified as independent predictors of poor OS. Both pre- and postoperative serum CA19-9 levels predict the survival of patients with resectable CC, and may contribute to the establishment of a new therapeutic strategy.