The goals of this study were (1) to compare, in a single institute, the clinical results of patients with newly diagnosed glioblastoma multiforme (GBM) treated with stereotactic radiosurgery (SRS), which has been incorporated into the initial management approach, with those in-patients treated with intra-operative radiotherapy (IORT) and (2) to assess whether these local irradiation boost therapies are prognostic factors on survival analysis. One hundred and twenty adult patients with supratentorial GBM had undergone tumour resection or biopsy and had received external beam radiotherapy (EBRT). Of them, 31 underwent IORT, 29 underwent SRS, and the remaining 60 had no local high-dose irradiation boost. The local irradiation boost led to clearly better results on survival of GBM patients. Furthermore, SRS is less invasive and allows for meticulous target planning of the irradiation boost, and was superior to IORT in terms of survival prolongation as well as suppression of local tumour recurrence/progression at the primary site in this series. In addition, SRS was a significant, positive prognostic factor for survival as well as gross-total resection of the tumour, and could be an alternative therapeutic modality to IORT for GBM.