Objective First-line therapy for low-grade gliomas (LGGs) is surgery, in some cases followed by radiotherapy and chemotherapy. Gamma Knife radiosurgery (GKRS) has gained more relevance in the management of these tumors. The aim of this study was to assess efficacy and safety of GKRS for treatment of LGGs. Methods Between 2001 and 2014, 42 treatments were performed on 39 patients harboring LGGs; 48% of patients underwent previous surgery, and 20.5% underwent previous radiotherapy. Mean tumor volume was 2.7 cm3, and median margin dose was 15 Gy. Results Mean follow-up was 60.5 months (range, 6–164 months). Actuarial progression-free survival was 74.9%, 52.8%, and 39.1% at 1 year, 5 years, and 10 years; actuarial overall survival was 97.4%, 94.6%, and 91.8% at 9 months, 1 year, and 5 years. Solid tumor control was achieved in 69.2% of patients, whereas cystic enlargement was recorded in 12.9% of cases. At last follow-up, volume reduction was recorded in 57.7% of cases, and median volume decreased by 33.3%. Clinical improvement was observed in 52.4% of patients. Karnofsky performance scale score was improved in 15 patients (45.5%), unchanged in 17 patients (51.5%), and worsened in 1 patient (3%). Mean posttreatment scores of 36-item short form health survey domains did not significantly differ from scores in a healthy Italian population. Conclusions This study confirms safety and effectiveness of GKRS for LGGs in controlling tumor growth, relevantly improving patients’ overall and progression-free survival. GKRS improved patients’ functional performance and quality of life, optimizing social functioning and minimizing disease-related psychological impact. © 2017 Elsevier Inc.