ObjectiveRadiotherapy is one of the effective ways to treat glioblastoma multiforme (GBM). We aimed to explore the prognostic difference between external beam radiotherapy (EBRT) and EBRT combined with brachytherapy (EBRT + BT).MethodsThe GBM patients from the Surveillance, Epidemiology, and End Results (SEER) database were divided into two cohorts: the EBRT cohort and the EBRT + BT cohort. Kaplan–Meier (KM) analysis and Cox proportional hazards regression were used to determine the underlying risk factors for overall survival (OS) and disease-specific survival (DSS). And the competing risk model and propensity score matching (PSM) was adopted to eliminate potential biases. We also conducted subgroup analyses and interaction tests as well.ResultsThere was a total of 41,010 eligible GBM patients. The median OS (15 months) and DSS (17 months) of the EBRT + BT cohort were significantly longer than that of the EBRT cohort (OS = 11 months, DSS = 12 months). After using the competing risk model and PSM, we found that only advanced age was the independent risk factor, while only EBRT + BT was the independent protective factor (HR = 0.84, 95%CI [0.74,0.96], p = 0.01). EBRT had universal effects in the treatment of GBM, and EBRT + BT had a more pronounced protective effect in the subgroups of males (HR = 0.81, 95%CI [0.68,0.97], p = 0.02) and local excision (HR = 0.82, 95%CI [0.34,0.95], p = 0.01).ConclusionsThe therapeutical effect of EBRT + BT treatment is better than that of EBRT alone, especially in male patients or patients who have undergone local resection. Our findings may provide novel evidence to develop a better radiotherapy strategy for GBM patients.