To evaluate the impact of H3K27M mutation in the prognosis of histological high-grade intramedullary astrocytoma.A total of 78 patients who were diagnosed with high-grade spinal cord astrocytoma were included. Clinical data consisting demographic, radiological, molecular features and treatment data were recorded. Univariate and multivariate Cox analysis were performed to investigate variables associated with survival outcome of histological high-grade spinal cord astrocytoma.Median survival time was 21 months. Overall survival (OS) at 1 and 3 years was 65.7% and 40.7%, respectively. Sex, location, and tumor span did not present significant association with OS. Patients with H3K27M mutation showed significant shorter duration of symptom than patients with H3K27 wild-type. As respect to adjuvant treatment, adjuvant radiotherapy and chemotherapy were associated with favorable OS (both p = 0.01). Younger patients (age ≤ 18 years) had shorter OS (p = 0.008) than adult patients (age > 18 years). Of note, H3K27M mutation did not show significant impact on the survival outcome, regardless of histology grade 3 or grade 4 (p = 0.3).Histological high-grade spinal cord astrocytoma has dismal prognosis. Our study demonstrated that H3K27M mutation did not show significant impact on survival outcome of histological high-grade spinal cord astrocytoma.