Yttrium‐90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000‐patient cohort acquired over a 15‐year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child‐Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention‐to‐treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty‐three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty‐eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5‐80.3) months, BCLC B 25.0 (CI, 17.3‐30.5) months, and BCLC C 15.0 (CI, 13.8‐17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21‐30.2) months, BCLC B 15.0 (CI, 12.3‐19.0) months, and BCLC C 8.0 (CI, 6.8‐9.5) months. Forty‐nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. Conclusion: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first‐line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).