Abstract: Objective: To analyze the prognostic value of carbohydrate antigen 125 (CA125) for pancreatic cancer patients with normal CA19-9. Methods: The clinical data of 182 pancreatic cancer patients with normal preoperative CA19-9 underwent radical resection at the Pancreatic Cancer Institute of Fudan University, Shanghai Cancer Center from March 2010 to December 2015 were retrospectively analyzed. The relationship between serum CA125 and clinicopathological characteristics was analyzed. Kaplan-Meier survival curve and multivariate Cox regression analysis were used to analyze the prognostic value of serum CA125 in patients. Results: Patients with higher preoperative serum CA125 level had worse tumor differentiation (P=0.013) and lymph node metastasis (P=0.016). The median over survival (OS,16.8 months) and recurrence-free survival (RFS, 10.4 months) of patients with higher level of serum CA125 before surgery were significantly shorter than those of patients with lower level of preoperative serum CA125 (OS:>24.3 months, P<0.001; RFS:16.3 months, P=0.001). Multivariate Cox regression analysis results showed that high level of preoperative serum CA125 level was an independent predictor of short OS (hazard ratio=2.171, 95% confidence interval 1.229-3.836, P=0.008) and RFS (hazard ratio=1.648, 95% confidence interval 1.114-2.438, P=0.012) in pancreatic cancer patients with normal preoperative serum CA19-9 level. Conclusions: Preoperative serum CA125 level is an independent prognostic factor for pancreatic cancer patients with normal preoperative serum CA19-9 level, which would provide evidence for the selection of postoperative adjuvant treatment strategies.