Purpose: It has recently been reported that serum CA-125 levels may serve as a prognostic indicator of extravesical disease in patients with bladder cancer. This study evaluated the role of CA-125 as a prognostic marker in patients with transitional cell carcinoma of the bladder undergoing radical cystectomy and urinary diversion. Methods: Ninety-two consecutive patients underwent planned radical cystectomy and urinary diversion with curative intent (2005-2006). Serum CA-125 levels were obtained in all patients and correlations were made to clinical and operative findings and pathological outcomes. Outcomes were evaluated with regard to normal vs. abnormal CA-125 values and with regard to absolute values of CA-125 levels. Results were also stratified by short-term recurrence rates. Results: Mean CA-125 values varied significantly by pathological stage and by resectability. No patient (0/56) with organ-confined disease (≤pT2N0) had an abnormal CA-125, and only 1 patient (1/75 = 1.3%) with ≤pT3N0 disease had an abnormal value. Conversely, 35% of patients with regionally-advanced disease (pT4 or N+) had an elevated CA-125, and all patients with unresectable disease (5/5) had an elevated value. In addition, patients with abnormal values of CA-125 (i.e., <35 U/ml) had a significantly higher upstaging rate compared to non-upstaged patients (18.8% vs. 3.5%, respectively; P = 0.0233). As well, patients with CA-125 levels <15 U/ml had a significantly higher upstaging rate compared with non-upstaged patients (53.1% vs. 15.8%, respectively; P = 0.0005). At a mean follow-up of 15 months (median = 14 months), patients with T2/T3N0 disease who recurred had a higher mean value than patients with pT2/T3 disease who did not recur (20.1 vs. 10.8 U/ml). Conclusions: Serum CA-125 levels may serve as a useful predictor of pathological outcomes in patients undergoing cystectomy for urothelial carcinoma of the bladder. Further studies will be carried out to determine the predictability of CA-125 on long-term recurrence and survival rates, and to evaluate the utility of CA-125 as a marker for disease response in patients with recurrent or advanced disease undergoing systemic therapy. © 2009 Elsevier Inc. All rights reserved.