Purpose To report our results of image-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the primary treatment of patients with inoperable glioblastoma multiforme (GBM) in the pre-temozolomide period. Material and methods Between 1994 and 2004, 17 patients were treated with HDR BRT for inoperable GBM. Of those, only 11 patients were treated with IRT BRT, and the remaining six patients received combined IRT BRT and external beam radiotherapy (EBRT). Patient's median age was 59.3 years (range, 29-83 years) and median tumor volume was 39.3 cm3 (range, 2-162 cm3). The prescribed HDR dose was median 40 Gy (range, 30-40 Gy), delivered twice daily in 5.0 Gy fractions over four consecutive days. Survival from BRT, toxicity as well as the impact of several prognostic factors was evaluated. Results At a median follow-up of 9.3 months, the median overall survival for the whole population, after BRT alone, and combined BRT with EBRT was 9.3, 7.3, and 10.1 months, respectively. Of the prognostic variables evaluated in univariate analysis, i.e., age, Karnofsky performance score, BRT dose, and tumor volume, only the latter one reached statistical significance. Two patients (11.7%) developed treatment-associated adverse events, with one (5.8%) symptomatic radionecrosis and one (5.8%) severe convulsion episode, respectively. Conclusions For patients with inoperable GBM, IRT HDR BRT alone or in combination with EBRT is a safe and effective irradiation method providing palliation without excessive toxicity.