BACKGROUND It has been previously reported that CD155 is often over-expressed in a variety of cancer types. In fact, it is known to be involved in cancer development, and its role in cancer has been widely established. However, clinical and mechanistic studies involving CD155 yielded conflicting results. Thus, the present study aimed to evaluate overall prognostic value of CD155 in cancer patients, using a comprehensive analysis. METHODS Online databases were searched, data was collected, and clinical value of CD155 was evaluated by combining hazard ratios (HRs) or odds ratios (ORs). RESULTS The present study involved meta-analysis of 26 previous studies that involved 4325 cancer patients. These studies were obtained from 25 research articles. The results of the study revealed that increased CD155 expression was significantly associated with reduced OS in patients with cancer as compared to low CD155 expression (pooled HR = 1.772, 95% CI = 1.441-2.178, P < 0.001). Furthermore, subgroup analysis demonstrated that the level of CD155 expression was significantly associated with OS in patients with digestive system cancer (pooled HR = 1.570, 95% CI = 1.120-2.201, P = 0.009), hepatobiliary pancreatic cancer (pooled HR = 1.677, 95% CI = 1.037-2.712, P = 0.035), digestive tract cancer (pooled HR = 1.512, 95% CI = 1.016-2.250, P = 0.042), breast cancer (pooled HR = 2.137, 95% CI = 1.448-3.154, P < 0.001), lung cancer (pooled HR = 1.706, 95% CI = 1.193-2.440, P = 0.003), head and neck cancer (pooled HR = 1.470, 95% CI = 1.160-1.862, P = 0.001). Additionally, a significant correlation was observed between enhanced CD155 expression and advanced tumor stage (pooled OR = 1.697, 95% CI = 1.217-2.366, P = 0.002), LN metastasis (pooled OR = 1.953, 95% CI = 1.253-3.046, P = 0.003), and distant metastasis (pooled OR = 2.253, 95% CI = 1.235-4.110, P = 0.008). CONCLUSIONS Altogether, the results of the present study revealed that CD155 acted as an independent marker of prognosis in cancer patients, and it could provide a new and strong direction for cancer treatment.