We investigated the risk factors for diffuse midline gliomas of the spinal cord (DMGSCs). Seventy patients with spinal cord gliomas in two hospitals were analyzed retrospectively. Sixty-nine patients that underwent surgery achieved partial or gross total removal. The patients were subdivided into some groups, based on age, WHO grade, tumor location within the cord, tumor size, and molecular profile: immunohistochemical expression of p53 and ATRX, and mutational status of Histone 3 (H3), and BRAF. Thirty-three patients had an H3 K27M mutation (47%). Some clinical characteristics were significantly different between H3 K27M mutant and H3 wild-type tumors. The main risk factors for DMGSCs were male sex, glioblastomas, and ≤ 2 spinal cord segments. The median survival period of patients with H3 K27M mutant tumors was significantly shorter than those with H3 wild-type tumors (17.0 ± 3.7 months vs censored, P < 0.0001). In the DMGSC subgroup, patients with thoracic cord tumors had a significantly better prognosis than those with cervical cord tumors (31.0 ± 6.0 vs 10.0 ± 4.8 months). Patients > 45 years of age survived significantly longer than patients < 19 years (P = 0.001). In conclusion, H3 K27M mutation significantly predicts a worse outcome of spinal cord gliomas. Anatomical location and age are the main risk factors for DMGSCs. © 2021 Japanese Society of Neuropathology