<p>The management of large metastatic brain tumors (METs), particularly those in the posterior fossa (pf-METs), is challenging. While surgery can alleviate symptoms, it carries the risk of complications such as leptomeningeal disease (LMD). Upfront hypofractionated Gamma Knife radiosurgery (hf-GKRS) has shown promise as an alternative approach for managing large METs. This study assesses the efficacy and safety of upfront hf-GKRS for treatment-naïve large pf-METs. In this retrospective, single-center study, 40 patients with 42 pf-METs received hf-GKRS from October 2017 to June 2024. Patients eligible for the study were 18 years or older, had histologically confirmed malignancy, large pf-METs (&gt; 4 cm³), and a minimum of two follow-up MRI scans. The primary outcome was local control (LC), with secondary assessments of distant intracranial failure (DICF), intracranial progression-free survival (PFS), overall survival (OS), and toxicity. LC was achieved in 88.1% of pf-METs over a median follow-up of 6 months (mean: 13.7 months). LC rates at 6, 12, and 24 months were 95.8%, 95.8%, and 74.5%, respectively. Local failure (LF) occurred in 11.9% of cases, with a median recurrence time of 12 months. DICF was noted in 35% of patients, while no cases of LMD were reported. Intracranial PFS rates at 6, 12, and 24 months were 54.1%, 39.0%, and 16.7%, respectively, with a median PFS of 8 months. Symptomatic hydrocephalus developed in one patient (2.5%). Controlled primary tumor status (HR: 0.17, <i>p</i> = 0.036) was significantly associated with lower risk of death, while no other parameters were predictive of LC, DICF, or intracranial PFS. hf-GKRS demonstrates strong efficacy and safety as a primary treatment for selected, treatment-naïve large pf-METs over a relatively short follow-up duration. Further studies are warranted to refine patient selection, fractionation, and dosing strategies for this challenging population.</p>