© 2016 International Hepato-Pancreato-Biliary Association Inc. Background The ideal adjuvant therapy for resected cholangiocarcinoma remains controversial. National guidelines stratify recommendations based on margin status, though few studies are currently available for reference. Methods Data was abstracted on all patients with definitive resections of cholangiocarcinoma at our institution between 2000 and 2013. Adjuvant chemoradiation consisted of 45 Gy delivered to elective nodal regions and 50.4–54 Gy to the surgical bed with concurrent fluoropyrimidine-based chemotherapy. Subgroup analyses were performed delineated by margin status. Results Curative resection was performed on 95 patients followed by adjuvant chemoradiation in 23/95 (24%) and observation in 72/95 (76%) with a median follow-up of 21.7 months. For those receiving adjuvant chemoradiation the median overall survival was 30.2 months compared with 26.3 months for those observed (p = 0.0695). In a multivariable model controlling for other prognostic factors, adjuvant chemoradiation was associated with improved disease-free survival (HR 0.50, p = 0.03) and overall survival (HR 0.37, p = 0.004). In multivariable models stratified by margin status, adjuvant chemoradiation was associated with improved overall survival following both margin-negative (HR 0.34, p = 0.035) and margin-positive (HR 0.15, p = 0.003) resections. Conclusions Overall survival was improved with adjuvant chemoradiation following either margin-negative or margin-positive resections, which is not currently reflected in national guidelines.