CD155 is expressed in many types of human cells and has diverse functions. We herein evaluated the clinical importance of CD155 in pancreatic cancer.We investigated CD155 expression in 134 patients with pancreatic cancer, and evaluated the correlations of CD155 with prognosis, tumor immunity and angiogenesis. Furthermore, CD155 functions were examined.CD155 expression was abundant in pancreatic cancer tissues. Patients with high CD155 expression had poorer postoperative prognosis than those with low expression. Multivariate analysis indicated that CD155 expression had a significant independent prognostic value. Tumor CD155 expression inversely correlated with the presence of tumor-infiltrating lymphocytes. Furthermore, it significantly positively correlated with vascular endothelial growth factor expression and intra tumoral microvessel density. In addition, silencing of CD155 inhibited proliferation, and induced cell-cycle arrest at G2/M phase in pancreatic cancer cells.CD155 may play a critical role through both immunological and non-immuno logical mechanisms in pancreatic cancer and may be a therapeutic target for this intractable malignancy.