PURPOSE: There are few data on radioembolization in the setting of biliary obstruction. The present study was performed to assess the safety of yttrium-90 ((NY)-N-90) radioembolization in the setting of tumor-related biliary obstruction and total bilirubin levels of 2 mg/dL or lower. MATERIALS AND METHODS: Twelve patients with liver tumors underwent 19 treatment sessions with Y-90 to the obstructed liver lobe or segment. Initial bilirubin level was 2 mg/dL or lower in all cases. Measured outcomes included pre- and posttreatment white blood cell (WBC) count, total bilirubin level, and alkaline phosphatase (ALP) level. Bilirubin toxicities and biliary complications were assessed according to Common Toxicity Criteria, version 3.0. RESULTS: Lobar or segmental Y-90 was successful in all cases. Pre- and posttreatment median WBC counts (5.3 vs 5.3; P = .490), bilirubin levels (1.0 vs 1.1; P = .460), and ALP levels (195 vs 146; P = .712) showed no differences. One case of grade 3 bilirubin toxicity was noted in a patient with liver hilar nodal progression and subsequent biliary obstruction requiring external drainage. Complete resolution of biliary obstruction was seen after Y-90 treatment in one case of metastatic colorectal carcinoma at 1 month follow-up. No biliary complications (infection, sepsis, biliary necrosis, biloma formation, abscess development, or biliary stricture) were encountered in this cohort during an overall median follow-up time of 22.9 months. CONCLUSIONS: The use of Y-90 glass microspheres demonstrated a good safety profile in the setting of tumor-related biliary obstruction in patients with normal or near-normal bilirubin levels in this series, without evidence of therapy-related progressive leukocytosis, bilirubin increase, or infectious or biliary complications after treatment.