BACKGROUND The significance of programmed death ligand 1 (PD-L1) expression in the prognosis of patients with colorectal cancer remains to be determined. METHODS We assessed the levels of PD-L1 expression in tumor-infiltrating immune cells as well as tumor cells, and evaluated the association between PD-L1 expression and clinical outcome in 262 colorectal cancer patients. RESULTS In univariate analysis, TNM stage (p < 0.001), PD-L1 expression in tumor-infiltrating immune cells (p = 0.016), tumor location (p = 0.033), and tumor size (p = 0.019) were associated with survival. In multivariate analysis, PD-L1 expression in tumor infiltrating immune cells and TNM stage were independent prognostic factors (HR 1.83, 95 % CI 1.09-3.05, p = 0.021; HR 2.49, 95 % CI 1.51-4.12, p < 0.001, respectively). Eight percent of patients had positive PD-L1 expression in tumor cells. In contrast, PD-L1 expression in tumor cells was not significantly associated with patient clinical outcome. CONCLUSIONS Our data indicate that PD-L1 status in tumor-infiltrating immune cells is a significant prognostic factor in colorectal cancer patients. There is a need for randomized studies that evaluate the role of PD-L1 expression in colorectal cancer in treatment decision protocols for novel immunotherapy.