No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib. Patients with ahistological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis. From January 2020 to December2022, 21patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8months (range 5-20). Median re-RT dose was 24 Gy (range 18-36 Gy) for amedian number of 5fractions (range 1-6). Median regorafenib treatment duration was 12weeks (range 3-26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6‑month overall survival (OS) from recurrence were 8.4months (95% confidence interval [CI] 6.9-12.7 months) and 75% (95% CI 50.9-89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6months (95% CI 3.7-8.5months). The most frequent side effects were asthenia that occurred in 10patients (8cases of grade2 and 2cases of grade3), and hand-foot skin reaction (2patients grade3, 3patients grade2). Adverse events led to permanent regorafenib discontinuation in 2cases, while in 5/21cases (23.8%), adose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization. For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is asafe treatment. Prospective trials are necessary.