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Background: The purpose of this study is to review the results of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal venous tumor thrombus (PVTT) in a Western patient population., Methods: Thirty-four patients with HCC PVTT treated from 2007 to 2014 with RT were identified. Biologically effective dose (BED) was calculated for each patient, and greater than the median dose delivered (75 Gray (Gy)) was evaluated as a potential prognostic factor. Survival was compared and independent prognostic variables were evaluated by a Cox proportional hazards regression model., Results: Twenty-six patients (76.5%) exhibited a radiographic response to RT, and 10 patients (29.4%) ultimately developed local failure. Local control, liver control, distant control and OS at one year were 57.1%, 36.4%, 55.2% and 57.4%, respectively. Patients who received a BED >75 Gy had a significantly better local control at 1 year (93.3% vs 45.6%; Log Rank p = 0.0184). Patients who received a BED >75 Gy also had significantly better median survival (24.7mo vs 6.1mo) and 1-year overall survival (76.5% vs 30.0%) when compared with BED ≤75 Gy (Log-Rank p = 0.002)., Conclusion: Our data suggest that RT should be considered for well-selected patients with HCC and PVTT for the purpose of improving local control and potentially prolonging the time to worsening venous obstruction and liver failure. When feasible, dose-escalation should be considered with a target BED of >75 Gy if normal organ dose constraints can be safely met.