OBJECTIVE Surgery is the mainstay treatment for transitional cell carcinoma (TCC) of the ureter; however, local recurrence remains a common cause of treatment failure for locally advanced disease after surgery, and the benefit of adjuvant radiotherapy has not been completely determined. The objective of this analysis was to evaluate the outcome of postsurgical high dose radiotherapy consisting of intraoperative electron beam radiotherapy (IOERT) and external beam radiotherapy (EBRT) in locally advanced transitional cell carcinoma of the ureter. METHODS Seventeen patients with pathologically diagnosed TCC of ureter were treated with nephroureterectomy and adjuvant radiation consisted of IOERT and EBRT according to an institutional research protocol. The dose of IOERT ranged between 10 to 20 Gy (median 14 Gy). Conventional EBRT given with the total dose ranged between 36 and 45 Gy (median 42 Gy). Chemotherapy was utilized in 10 of the 17 patients at the discretion of their primary oncologist. RESULTS The median follow-up for all patients was 48 months (range, 10-91 months). The overall survivals of the entire group of patients at 1, 3, and 5 years were 82%, 65%, and 46%, respectively. The estimated locoregional control rates at 1, 3, and 5 year were 82%, 64%, and 51%, respectively. Depth of invasion (pT), histological grade, and presence of residual disease were significant prognostic factors in univariate analysis. Multivariate analysis revealed that independent prognostic factors for survival included histological grade (grade 1 + 2 vs. grade 3 + 4; P = 0.03) and presence of residual disease after surgery (R0 vs. R1 or R2 resection; P = 0.053). Acute and long-term adverse effects rated grade 3 or higher were seen in 4 and 2 patients, respectively. No grade 5 toxicity occurred. CONCLUSIONS IOERT and EBRT following surgery produced a 51% local control and 46% overall survival rate for locally advanced TCC of ureter at 5 years of follow-up, with acceptable rates of acute and late toxicity. Adjuvant IOERT appears to permit dose escalation safely in patients who received conventional adjuvant EBRT and chemotherapy. This strategy deserves to be optimized and then tested in a prospective trial to learn if it can further improve outcome.