To examine the role of brachytherapy in the treatment of cholangiocarcinomas in a relatively large group of patients.Using the Surveillance, Epidemiology and End Results database, a total of 193 patients with cholangiocarcinoma treated with brachytherapy were identified for the period 1988–2003. The primary analysis compared patients treated with brachytherapy (with or without external-beam radiation) with those who did not receive radiation. To try to account for confounding variables, propensity score and sensitivity analyses were used.There was a significant difference between patients who received radiation (n = 193) and those who did not (n = 6859) with regard to surgery (p < 0.0001), race (p < 0.0001), stage (p < 0.0001), and year of diagnosis (p <0.0001). Median survival for patients treated with brachytherapy was 11 months (95% confidence interval [CI] 9–13 months), compared with 4 months for patients who received no radiation (p < 0.0001). On multivariable analysis (hazard ratio [95% CI]) brachytherapy (0.79 [0.66–0.95]), surgery (0.50 [0.46–0.53]), year of diagnosis (1998–2003: 0.66 [0.60–0.73]; 1993–1997: (0.96 [0.89–1.03; NS], baseline 1988–1992), and extrahepatic disease (0.84 [0.79–0.89]) were associated with better overall survival.To the authors' knowledge, this is the largest dataset reported for the treatment of cholangiocarcinomas with brachytherapy. The results of this retrospective analysis suggest that brachytherapy may improve overall survival. However, because of the limitations of the Surveillance, Epidemiology and End Results database, these results should be interpreted cautiously, and future prospective studies are needed.