Purpose <p>Pre-operative stereotactic radiosurgery (SRS) for brain metastases (BrM), an emerging alternative to post-operative SRS, is typically performed 1–2 days before resection. However, a longer period of the irradiated tumour in situ may confer anti-tumour immunological benefits. We conducted the first clinical trial to evaluate the feasibility of planned delayed resection after pre-operative SRS.</p> Methods <p>In this single-arm trial, patients with suspected BrM suitable for pre-operative SRS and surgery were eligible. The primary endpoint was feasibility of resection 7–21 days after SRS, with a pre-defined feasibility threshold of 66% receiving this. Secondary endpoints included 6-month adverse events (AE) and local control (LC) rates. Tumour volume change was assessed from SRS- and neurosurgery-planning MRI’s.</p> Result <p>78 patients were screened and the target accrual of 15 patients was met. Common reasons for pre-operative SRS ineligibility were lack of existing cancer diagnosis (44%) and tumour size/peri-tumoural oedema (18%). Two patients declined resection after SRS. The median SRS-to-surgery interval was 8 days (range 0–15). Nine tumours in 8 patients (56%) received delayed resection. Reasons for earlier resection were predominantly non-medical. There were no Grade &gt; 2 AE. The 6-month BrM LC was 100%. At a median follow-up of 13.8 months, the only BrM local failure after SRS and resection occurred with a 0-day SRS-to-surgery interval. No histopathological diagnosis issues were encountered with delayed resection. An increased SRS-to-surgery interval correlated with greater tumour shrinkage.</p> Conclusions <p>The pre-defined feasibility threshold for delayed resection was not met, but more than half of patients received delayed resection without safety concerns.</p> Trial registration number <p>ACTRN12622001372774 (Registered 26/10/2022).</p>