Background: Stereotactic radiotherapy (SRT) should be applied with a biologically effective dose with an α/β of 12 (BED12) ≥ 40 Gy to reach a 1-year local control (LC) ≥ 70%. The aims of this retrospective study were to report a series of 81 unresected large brain metastases treated with Linac-based multifraction SRT according to the ICRU 91 and to identify predictive factors associated with LC. Methods: Included in this study were the first 81 brain metastases (BM) consecutively treated with Linac-based volumetric modulated arc therapy (VMAT) multifraction SRT from 2017 to 2019. The prescribed dose was 33 Gy for the GTV and 23.1 Gy (70% isodose line) for the PTV in 3 fractions (3f). Mean BM largest diameter and GTV were 25.1 mm and 7.2 cc respectively. Mean follow-up was 10.2 months. Results: LC was 79.7% and 69.7% at 1 and 2 years respectively. Significant predictive factors of LC were GTV D98% (HR = 0.84, CI 95% = 0.75-0.95, p = 0.004) and adenocarcinoma as the histological type (HR = 0.29, CI 95% = 0.09-0.96, p = 0.042) in univariate and multivariate analysis. A threshold of 29 Gy for GTV D98% was significantly correlated to LC (1-year LC = 91.9% for GTV D98% ≥ 29 Gy vs 69.6% for GTV D98% < 29 Gy (p = 0.030)), corresponding to a BED12 = 52.4 Gy. No tumor progression was observed for a BED12 ≥ 53.4 Gy, corresponding to a GTV D98% ≥ 20 Gy /1f and GTV D98% ≥ 29.4 Gy 3f. Median OS was 15 months. Symptomatic radionecrosis occurred in 4.9% of cases. Conclusion: The GTV D98% is a strong reproducible significant predictive factor of LC for brain SRT. Dose prescription should lead to a GTV BED12 98% ≥ 52.4-53.4 Gy to significantly improve LC, corresponding to respectively a GTV D98% ≥ 19.7-20 Gy/1f and 29-29.4 Gy/3f.