The preoperative controlling nutritional status (CONUT) score and serum carbohydrate antigen 199 (CA199) levels are individually correlated with the prognosis of pancreatic ductal adenocarcinoma (PDAC). The objective of this study aimed to investigate the efficacy of CONUT score and CA199 (CONUT-CA199) combination in predicting the prognosis of PDAC patients undergoing radical surgery. Methods: We retrospectively analyzed the preoperative CONUT scores and serum CA199 levels of 294 patients with PDAC who underwent radical resection at the Affiliated Hospital of Southwest Medical University between March 2012 and July 2019. Patients were divided into four groups on the basis of their preoperative CONUT scores and serum CA199 levels: CONUT low /CA199 low (1), CONUT low /CA199 high (2), CONUT high /CA199 low (3), and CONUT high /CA199 high (4). The prognostic effects were compared among the groups. Results: CONUT high was more frequent in patients with positive peripancreatic infiltration and Clavien-Dindo classification of ≥IIIa (P < 0.001). Kaplan-Meier analysis revealed obvious difference in overall survival (OS) and recurrence-free survival (RFS) among patients with PDAC having CONUT-CA199 scores of 1, 2, 3 and 4 (P <0.001). Peripancreatic infiltration, lymph node metastasis, pTNM stage, CONUT score, serum CA199 levels, and CONUT-CA199 classification were found to be the independent prognostic factors for OS and RFS in multivariate analyses. In time-dependent receiver operating characteristic (ROC) analyses, the area of the CONUT-CA199 score under the ROC curve (AUC) was higher than that of the preoperative CONUT score or serum CA199 levels for the prediction of OS and RFS. Conclusion: CONUT-CA199 classification may be more effective in predicting the postoperative prognosis of PDAC patients