Objective: Treatment of H3K27M-altered midline gliomas is a significant challenge. This study aims to assess the efficacy of radiotherapy for these patients. Materials and Methods: Thirteen patients with histologically confirmed H3K27M-altered midline glioma, treated with radiotherapy +/- temozolomide be- tween 2019 and 2021, were retrospectively analyzed. Clinical and radiological responses, survival times, and prognostic factors were evaluated. All patients were treated with hypofractionated radiotherapy, with a dose of 25-40 Gy. Results: The median age was 42 years (ranging from 19 to 55). Karnofsky Performance Status scores ranged from 50 to 70, with a median score of 50. Hypof- ractionated radiotherapy was administered to all patients, with 25 Gy given in 5 fractions to 7 patients (53.8%), 39 Gy in 13 fractions to 3 patients (23.1%), and 40 Gy in 15 fractions to 3 patients (23.1%). Clinically, two patients (15.4%) showed symptomatic improvement, five patients (38.8%) remained stable, and six patients (46.2%) had neurological deterioration. Radiologically, one patient had a partial response, six patients (46.2%) had stable disease, and radiological progression occurred in three patients (23.1%). The median progression-free survival and median overall survival time were 123 and 154 days, respectively. Karnofsky Performance Status 50 was associated with a worse prognosis. Conclusion: These results suggest that the efficacy of radiotherapy might be limited for adults with H3K27M-altered midline gliomas with poor performance status. New studies are necessary for a more comprehensive understanding of effective therapeutic strategies.