Background: Gallbladder cancer is a highly fatal disease with a high rate of recurrence even when diagnosed at an early stage. Because of its relative rarity, there are currently no established algorithms to guide therapy after cholecystectomy. To explore the value of adjuvant therapy with chemotherapy and radiation, we evaluated patients with resected gallbladder cancer treated at our institution. Methods: Patients diagnosed with gallbladder cancer who underwent cholecystectomy (simple or radical) between 2000 and 2010 were identified using our cancer registry. Retrospective chart review was performed for clinicopathologic data, including age, stage, grade, type of surgery, margin status, and type and duration of adjuvant therapy. The primary endpoint was overall survival (OS). Univariate (UVA) and multivariate (MVA) analysis was performed with Cox logistic regression analyses. Results: We identified 73 patients with a median followup for all patients of 28.2 months. The majority of patients were female (74%) and underwent radical cholecystectomy (64%). Positive margins and adjuvant radiation therapy were documented in 21% and 37%, respectively. The majority of patients did not receive any adjuvant therapy (53.4%). Median OS for all patients was 41.3 months. There was a survival benefit associated with patients undergoing radical cholecystectomy followed by adjuvant radiation (median OS 48.4 months vs. 22.3 months; HR 0.35; 95% CI: 0.13–0.98; p=0.0448) compared to simple cholecystectomy alone. On UVA, increasing age and positive margins were significantly associated with worse OS, while radical cholecystectomy was associated with improved OS. On MVA, increasing age, male gender, poorly differentiated tumor, and positive margins were associated with worse OS, while adjuvant radiation was associated with improved OS (p=0.0113). Conclusions: Our analysis supports the role for adjuvant radiation therapy in resected gallbladder cancer. Multi-institutional prospective studies should be performed to evaluate the optimal treatment strategy. Biomarker analysis might also help determine the subset of patients who would benefit from combined chemoradiation.