Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is derived from a background of chronic inflammation from both viral and environmental factors. Recent data indicates that immune therapy efficacy is improved in virally mediated HCC. We sought to investigate what impact HCC etiology has on outcomes in patients treated with yttrium-90 (Y90). Methods: We conducted a retrospective review of patients with HCC treated at our institution with Y90 radiotherapy from 2005-2021. Clinical and treatment characteristics were recorded, including: age, stage, HCC etiology, performance status, Child Pugh class, liver mass/volume treated, dose, prior therapy, imaging characteristics and basic labs. Univariable (UVA) and multivariable analyses (MVA) were conducted to identify prognostic factors for local control (LC) and overall survival (OS) following Y90. Results: 67 patients and 196 distinct tumors treated with Y90 were identified. Median prescription dose was 110 Gy (range 44-157). Patients were stage I-IVB with the most frequent stages being II, IIIb and IIIa (34%, 21% and 19% patients, respectively). 49 patients (73%) were Child-Pugh A and 18 (27%) were Child-Pugh B. 5 patients only had hepatitis B (7%), 26 patients only had hepatitis C (39%), and 6 patients had both hepatitis B and C (9%). Median OS among all patients was 7.6 (95% CI 5.6-11.5) months following Y90. The LC rate of all treated lesions was 42% and 24% at 6 and 12 months, respectively. On UVA analysis, improved LC was associated with younger age (p=0.019), smaller liver mass (p=0.039), and Hepatitis B etiology (p=0.018). On Cox regression survival analysis, worsened OS was associated with lower ECOG status (p=0.024), advanced stage (p=0.023), lower albumin (p=0.001), higher AFP (p<0.001), and portal vein invasion/thrombosis (p=0.006, p=0.010). On MVA, lower albumin, higher AFP, advance stage and prior sorafenib were significantly related to worsened OS. If hepatitis B or C was forced into the MVA, the hazard ratio was 0.6 (95% CI 0.3-1.04) with p=0.068. Conclusions: Our results indicate that viral etiology impacts LC in our patients. Larger studies are necessary to confirm these results and to determine whether viral etiology impacts OS.