The present study was aimed to investigate the relationship between the expression of collagen type V alpha 2 chain (COL5A2) and clinical outcomes of patients with bladder cancer.Chi-square test and log-rank-based survival analysis were performed to assess the correlation of COL5A2 expression with clinical characteristics and survivals of patients with bladder cancer using GSE13507. Gene set enrichment analysis was conducted to study the relevant mechanisms.Bladder cancer patients in COL5A2 low expression group were associated with better invasiveness (P < .0001), tumor grade (P = .001), T staging (P < .0001), N staging (P = .002), cancer specific survival (P < .0001), overall survival (P < .0001), and a trend of better M staging (P = .053) than those in COL5A2 high expression group.COL5A2 might affect the progression of bladder cancer through "Coagulation," "Hypoxia," "Apical junction," "Ultraviolet response," "Epithelial mesenchymal transition," "Angiogenesis," "KRAS (KRAS proto-oncogene, GTPase) signaling,""Complement,""IL2-STAT5-signaling," "Inflammatory response," "IL6-JAK-STAT3-signaling," "Myogenesis," "TNF α signaling," "Apoptosis," and "Hedgehog-signaling."Our results demonstrated that COL5A2 was correlated with poor clinical outcomes and survivals of patients with bladder cancer, suggesting that it could be regarded as a biomarker of bladder cancer.