Background: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for these. CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. Methods: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) on transurethral resection of bladder tumor (TURBT) who subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by immunohistochemistry in both TURBT and matched RC specimens. Expression levels ≥1% were considered positive. The difference between CD47 expression levels between TURBT and RC were also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes were evaluated by Person’s chi-squared test and Kaplan-Meier method respectively. Results: A total of 87 MIBC patients were included. The median age was 66 (39-84) years. The majority of patients were Caucasian (95%), male (79%), and age > 60 (63%). Most patients (75%) underwent NAC prior to RC. Of those who received NAC, 35% were responders and 64% were non-responders. Responders includes those with a pathologic complete response (T0) or partial response (Tis or T1); non-responders included those with stage ≥ T2. The final reported stages for all patients were as follows: stage 0 (32%), stage I (1%), stage II (20%), stage III (43%), and stage IVA (5%). 60% of patients were alive, 40% died from bladder cancer, and 30% had disease recurrence at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients > 60 (p = 0.006), non-responders (p = 0.002), stage ≥ III (p < 0.001) were associated with worse OS by univariate analysis. There was no significance with multivariate analysis. There was a slight positive trend for decreased CD47 levels between TURBT and RC in patients who received NAC (p = 0.5), though this did not reach statistical significance. Conclusions: CD47 expression is not a prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore a potential role for anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend between decreased CD47 levels (from TURBT to RC) in patients receiving NAC. More research is needed to understand how NAC may or may not modify immune surveillance mechanisms in MIBC.