Background: To evaluate the association between pre-cystectomy carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA) levels and pathologic stage and oncological outcome of urothelial carcinoma of bladder (UCB). Methods: Preoperative stored serum samples of 186 patients with UCB who underwent radical cystectomy at USC between 2004 and 2009 were randomly selected to measure CA19-9, CA125, and CEA levels. Laboratory cut-off point values were used to define abnormal marker levels (CA 19-9>35.5, CA125>35.5, CEA>3.8). Pathologic stage was categorized as organ confined (OC) (pT1,T2), extravesical (EV) (>pT2), and lymph node positive (LN+) UCB. Cox regression model was used to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). Results: The mean age of patients were 70 years (ranges, 36-91) and the median follow-up was 4 years (ranges, 0.1–7). 94 (50.5%) patients had OC, 45 (24%) had EV, and 47 (25.5%) had LN+UCB. The mean CA 19-9, CA125, and CEA levels were14 (0.6–278) U/mL, 11.8 (3–79) U/mL, and 2.3 (0.3–30) ng/mL. 30/186 (16%) patients had at least one abnormal marker. Percentage of abnormal CA19-9 was significantly higher in locally advanced UCB (EV and/or LN+) compared to OC UCB (85.7% vs. 48%; P=0.03). The percentage of abnormal CA125 and CEA levels were comparable between locally advanced and OC UCB.4-year RFS and OS were 66% and 65%, respectively. After controlling for pathologic stage, age, and adjuvant chemotherapy; Abnormal CA19-9 and CEA were independent predictors of worse 4-year OS (HR:2.7; P=0.04 and HR:2; P=0.03). Abnormal CA 19-9 was also an independent predictor of worse 4-year RFS (HR: 2.8; P=0.05). Pre-cystectomy CA 125 level had no correlation with oncological outcome. Conclusions: In patients with UCB, abnormal precystectomyserumCA19-9 is correlated with advanced pathological stage and is an independent predictor of worse oncological outcome. Precystectomy CEA and CA 125 showed no significant correlation with pathological stage and oncological outcome. Prospective studies are encouraged to elucidate the clinical value of these serum markers.