Type 2 diabetes mellitus (DM) and obesity are known risk factors for poor outcomes in patients with systemic malignancies but are not well-studied in the brain tumor population. In this study we asked if type 2 DM and elevated body mass index (BMI) are independent risk factors for poor prognosis in patients with high-grade glioma (HGG.). We conducted a retrospective cohort study of 171 patients surgically treated for HGG at a single institution. BMI and records of pre-existing type 2 DM were obtained from medical histories. Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P < 0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. Mean age at diagnosis was 55.0 ± 17.3 years. Fifteen (8.8%) patients had a history of type 2 DM. Fifty-eight (35.8%) patients had a BMI < 25, 55 (34.0%) BMI 25-30, and 49(30.2%) BMI > 30. Radiation therapy, temozolomide, and higher KPS score were independently associated with prolonged survival while increasing age was associated with decreased survival. DM (P = 0.001) and increasing BMI (P = 0.003) were found to be independently associated with decreased survival. Diabetics had a decreased median overall survival (312 vs. 470 days, P = 0.003) and PFS (106 vs. 166 days, P = 0.04) compared to non-diabetics. Increasing BMI (<25, 25-30, and >30) was also associated with decreased median PFS: 195 vs. 165 vs. 143 days, respectively. Pre-existing DM and elevated BMI are independent risk factors for poor outcome in patients with HGG.