Simple SummaryStereotactic body radiotherapy (SBRT) using direct magnetic resonance (MR) guidance is a comparably new technology and enables ablative treatment of liver metastases without invasive placement of fiducials. We aimed to evaluate long-term clinical outcome. Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation based on the daily anatomy). The most prevalent fractionation scheme was 50 Gy in five fractions. Estimated local control of the irradiated liver metastases was 75% at 2 years and overall survival was 57% at 2 years. We report the largest patient cohort to date, demonstrating promising long-term clinical results for SBRT of liver metastases applying MR-guidance.Abstract(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC was 34% and 15%, PFS was 21% and 5% and OS was 83% and 57%. Two-year LHC was higher in case of BED > 100 Gy (100% vs. 57%; log-rankp= 0.04). Acute grade 1 and 2 toxicity (mostly nausea) occurred in 26% and 7% of the patients, with no grade ≥ 3 event. (4) Conclusions: To our knowledge, this is the largest cohort of MR-guided liver SBRT. Long-term local control was promising and underscores the aim of achieving >100 Gy BED. Nonetheless, distant tumor control remains challenging.