Purpose To evaluate the influence of bridging local-regional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and overall survival after orthotopic liver transplantation and to identify factors that predict HCC recurrence after orthotopic liver transplantation. Materials and Methods The United Network for Organ Sharing database was used to identify patients with HCC who underwent liver transplantation between 2002 and 2013. Patients with complete explant data within the Milan criteria for whom a Model for End-Stage Liver Disease exception was approved were retrospectively analyzed. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazard models to assess independent prognostic factors for overall survival. Propensity-matched analysis for treatment groups was performed to minimize selection bias. Results The rate of tumor recurrence after liver transplantation was 11.5% (321 of 2794), which significantly decreased overall survival (P < .001). The bridging LRT group exhibited lower recurrence (59 of 686 [8.6%]; P = .02) and longer median overall survival (75.9 months; P < .001). Recurrence was higher in patients older than 60 years, serum α1-fetoprotein greater than 400 mg/L, bilobar distribution, multiple lesions, absent necrosis, microvascular invasion, and tumors beyond the Milan criteria (P < .05). Age, LRT status, serum α1-fetoprotein, and microvascular invasion were independent risk factors (P < .05). In the matched cohort, similar factors that predicted recurrence were observed (P < .05), whereas bridging LRT (P = .03) and serum α1-fetoprotein (P = .02) were independent risk factors for recurrence. Conclusion LRT significantly decreased tumor recurrence and lengthened overall survival. © RSNA, 2016.