The aims of the present study were to clarify the prognostic value of peripheral blood variables in patients with pancreatic ductal adenocarcinoma (PDAC), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), and to determine the association between these variables and S100 calcium-binding protein A4 (S100A4) expression in tumor tissue, which is another prognostic factor for PDAC. Patients with PDAC were recruited at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between December 2008 and December 2014. A retrospective analysis was performed based on the recorded pre-treatment hematological parameters and clinical data. The prognostic value of NLR, PLR and LMR was examined. The association between these variables and S100A4 tissue expression was analyzed. Descriptive statistics and χ2 analyses were used in the present study. The median overall survival (OS) time of patients with PDAC was 9 months (range, 1–32 months). Univariate analysis revealed that NLR, LMR, carbohydrate antigen 19-9, surgery, chemotherapy, stage at diagnosis, tumor grade and age significantly affected OS. Although PLR exhibited no significant effects on OS, NLR and LMR were independent prognostic factors according to the multivariate analysis. Unpaired Student's t-test revealed differences between S100A4 expression and NLR, PLR and LMR. The results of the present study indicated that low NLR and high LMR were associated with a favorable prognosis in patients with PDAC. As a simply obtained and widely available index at diagnosis, NLR and LMR may become a novel predictive and classifying marker for PDAC in the clinical setting.