BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with a poor 5-year survival rate (5%-10%). ERCP-directed radiofrequency ablation (RFA) or photodynamic therapy (PDT) can be performed as palliative therapy for unresectable CCA. ERCP with PDT is associated with improved survival compared with stent placement alone. However, ERCP-directed RFA has not been directly compared with PDT in patients with CCA. OBJECTIVE: To compare overall survival in patients with unresectable CCA who underwent palliative ERCP-directed RFA versus PDT. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Forty-eight patients with unresectable CCA who underwent ERCP-directed ablative therapy for palliation of unresectable CCA. INTERVENTIONS: ERCP-directed RFA or PDT. MAIN OUTCOME MEASUREMENTS: Overall survival by Kaplan-Meier analysis after initial treatment with either RFA or PDT. RESULTS: Patients who underwent RFA (n = 16) demonstrated an overall survival similar to that of those who underwent PDT (n = 32), with a median survival of 9.6 versus 7.5 months, respectively (P = .799). Patient age (P = .45), sex (P = .52), and lead time (P = .59) from presentation to initial RFA or PDT had no significant association with survival. The presence of distant metastasis was inversely associated with survival (hazard ratio 3.55; 95% confidence interval, 1.29-9.77; P = .014). Patients who underwent RFA (compared with PDT) had a lower mean number of plastic stents placed per month (0.45 vs 1.10, P = .001) but also had more episodes of stent occlusion (0.06 vs 0.02, P = .008) and cholangitis (0.13 vs 0.05, P = .008) per month. LIMITATIONS: Retrospective, single-center design. CONCLUSIONS: Survival after ERCP-directed RFA and PDT was not statistically different in patients with unresectable CCA. A randomized, controlled trial is warranted to validate these preliminary results.