293 Background: Local-regional recurrences (LF) after radical cystectomy with or without chemotherapy are common in patients with locally advanced disease. Adjuvant radiation (RT) could reduce LF, but toxicity discouraged its use. Modern RT with reduced morbidity has rekindled interest but requires knowledge of pelvic failure patterns to design appropriate clinical target volumes. Methods: 5-yr LF rates after radical cystectomy plus pelvic lymph node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 patients with urothelial carcinoma of the bladder. The impact on the pattern of failure of pathologic stage, margin status, nodal involvement, and extent of node dissection was assessed using competing risk statistical methods. The percentage of patients whose sites of LF would be completely encompassed within various hypothetical clinical target volumes for post-operative radiation were calculated. Results: Stage pT3-4 patients had higher 5-yr LF rates in virtually all pelvic sites compared to pT0-2 patients. Among pT3-4 patients, margin status significantly altered the pattern of failure while extent of node dissection and pathologic nodal involvement did not. Stage pT3-4 patients with negative margins failed predominantly in the iliac/obturator nodes. Failures in the cystectomy bed and presacral region were significantly higher in pT3-4 patients with positive rather than negative margins. 76% of pT3-4 patients with negative margins who failed would have had all sites of LF included within clinical target volumes encompassing the iliac/obturator nodes, but only 57% of pT3-4 patients with positive margins would have their LF sites covered by such target volumes. Including the cystectomy bed and presacral region in the clinical target volume when margins were positive increased the percentage of encompassed failures to 91%. Conclusions: In adjuvant RT protocols, the obturator and iliac regions should be targeted in pT3-4 tumors with negative margins; coverage of presacral region and cystectomy bed is advised for pT3-4 with positive margins.