The purpose of this study was to evaluate the safety, efficacy, and survival following radioembolization (Y90) for unresectable intrahepatic cholangiocarcinoma (ICC). Our hypothesis was Y90 would provide high antitumor response with a tolerable safety profile. An IRB-approved retrospective analysis was performed in 138 consecutive patients with ICC treated with Y90 from 2004 to 2020. Primary outcomes were clinical and biochemical toxicities by CTCAE (version 5.0) and tumor response by World Health Organizing (WHO) criteria. Secondary outcomes were time-to-progression (TTP) and overall survival (OS) by the Kaplan-Meier method with censoring to resection/transplantation. Univariate and multivariate survival analyses were performed with log-rank tests and Cox proportional-hazards model, respectively. Baseline characteristics included solitary tumor in 56 (40.6%), unilobar distribution in 59 (42.8%), tumor burden < 25% in 96 (69.6%), extrahepatic disease in 48 (34.8%), and prior chemotherapy in 56 (40.6%). Grade 3+ clinical toxicities occurred in 10 (7.5%). Grade 3 bilirubin and alkaline phosphatase toxicities occurred in 4 (3.2%) and 2 (1.6%), respectively. Best response rates (WHO) were complete response in 3 (2.3%), partial response in 46 (34.9%), stable disease in 74 (56.1%), and progressive disease in 9 (6.8%) patients. Median index lesion TTP was not reached. Median intrahepatic TTP and extrahepatic TTP were 5.9 months (95% CI, 4.1-8.4) and 13.1 months (95% CI, 7.4-19.6), respectively. Eleven patients (8.0%) were downstaged to resection with OS of 41.8 months (95% CI, 16.1-NE). Additionally, three patients (2.2%) were transplanted. Median time to recurrence was 26.6 months (95% CI, 4.4-NE). Median OS for the entire cohort was 13.8 months (95% CI, 10.5-16.0). On multivariate OS analysis, solitary ICC (P< 0.001), no prior chemotherapy (P = 0.02), tumor burden < 50% (P = 0.03), no tumor thrombus (P = 0.004), and higher serum albumin (P = 0.01) were positive prognosticators. Y90 has an acceptable safety profile in a large cohort of patients with heterogenous treatment history and disease burden. High local disease control rates and downstaging in select patients supports the therapeutic role of Y90 for unresectable ICC.