BackgroundUsing data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.MethodsWe analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).ResultsAll-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p= 0.0045), 1 tumour nodule (0.0081),  > 1 TARE treatment (p= 0.0224), no prophylactic embolization (p= 0.0211), partition model dosimetry (p= 0.0007) and unilobar treatment target (0.0032). For ICC,  > 1 TARE treatment was associated with an increase in AEBS (p= 0.0224), and for colorectal liver metastases, ECOG 0 (p= 0.0188), > 2 prior systemic treatments (p= 0.0127), and 1 tumour nodule (p= 0.0155) were associated with an increased AEBS.ConclusionOur study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00270-023-03391-4.