To investigate whether protein expression of cyclooxygenase 2 (COX2) is associated with tumor phenotype, immunohistochemical alterations, and clinical outcome in urinary bladder cancer (BC). Tissue microarrays (n = 776) were used to analyze COX2, P53 and the Ki-67 labeling index immunohistochemically. A monoclonal mouse antibody was used after heat-induced antigen retrieval. COX2 expression was scored semiquantitatively (0-3+). COX2 expression was detected in 60% (368/617) of urothelial BC. Positive COX2 staining was seen in 77.8% (140/182) of muscle invasive urothelial BC, compared to 35% (7/20) of muscle invasive squamous cell carcinomas (p < 0.001). COX2 protein expression was associated with advanced tumor stage (p < 0.0001), high-grade histology (p < 0.0001), solid growth pattern in invasive BC (pT1-4, p = 0.02), high Ki-67 labeling index (p < 0.0001), and positive P53 IHC (p < 0.001). COX2 expression was not associated with survival, recurrence, and progression in clinically relevant subgroups (pTa, pT1, pT2-4). Expression of COX2 is common in advanced BC with poor prognostic characteristics, supporting efforts to initiate clinical trials on the efficacy of COX2 inhibitors in the adjuvant treatment of high-risk urinary BC.