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497 Background: Treatment approaches combining anti-angiogenic therapy with chemotherapy have shown promising clinical results in metastatic bladder cancer (BC). In order to interrogate the potential clinico-pathologic and molecular basis of these findings, we evaluated VEGFR2, vascular density and molecular subtyping in a series of BC patients. Methods: A custom-TMA with primary BC tissues from 117 patients (mean age 71 yrs; range 38-99 yrs; M:F = 83:34) treated at a single institution, was stained and scored (0-3) for CD34 (vascular density) and for VEGFR2 on tumor vessels and cells. CK5/6 and GATA3 IHC was scored by a pathologist to identify main molecular classes of BC. The association between clinico-pathologic variables, VEGFR2, CD34 and molecular subtypes was analyzed by Fisher’s exact test and ANOVA. Univariate and multivariate Cox proportional models were used for survival analysis. Results: Of 112 analyzable BC tissues, 41% were muscle-invasive (MIBC) vs. 56% non-muscle invasive (NMIBC) and 3% undetermined. Compared to NMIBC patients those with MIBC had shorter overall survival (p < 0.001). The main molecular subtypes included basal (11%), mixed baso-luminal (28%) and luminal (61%). Compared to luminal and baso-luminal subtypes, the majority of basal BCs were muscle invasive (p = 0.036). VEGFR2 expression was higher in tumor vessels but variable in tumor cells. 74% of BCs showed high-medium levels of VEGFR2 (scores 3-2) in tumor vessels and 88% had high-medium levels of tumor vascular density. Within basal, luminal and baso-luminal subtypes, 58%, 78% and 71% had high-medium levels of vascular VEGFR2 (p = 0.52), while 83%, 91% and 82% had high-medium levels of tumor vascular density (p = 0.08). Survival analyses showed increasing patient age, higher stage and lower VEGFR2 levels as independent predictors of shorter survival. Conclusions: Given the observed complexity of BC regarding VEGFR2 expression and vascular density across molecular subtypes, further investigation is warranted to understand how the frequent expression of VEGFR2 on tumor vasculature and variable expression in tumor cells relates to the efficacy of anti-angiogenic agents across these subtypes in bladder cancer.