Objectives: Intraoperative radiotherapy (IORT) is the delivery of ionizing radiation to the tumor or tumor bed during surgery. It is being explored as a treatment modality for brain metastases (BrMs). We aimed to determine the safety and efficacy of IORT for BrMs by reviewing the current evidence. Methods: We performed a systematic review of the online databases for studies on IORT for BrMs. Data on clinical features, treatment modalities, and outcomes were collected. Results: Five studies (n=179) were included. Mean age was 60.4 years, 43% were women. The most common etiology of BrMs were lung, melanoma, breast, and renal cancer. Ninety-five patients underwent IORT with the Photon Radiosurgery System (PRS) while 84 were treated with the INTRABEAM system. Follow-up ranged from 5 days to 94 months. The most frequent complication was radiation necrosis. Local recurrence and distal progression were seen in 11-77% and 0-82%, respectively. The 6- and 12-month overall survival ranged from 60-86% and 34-73%, respectively. Conclusion: The results of the systematic review on the safety and efficacy of IORT on BrMs were inconclusive, due to heterogeneity of the studies. Larger prospective studies are needed to determine the optimal dose, efficacy, and safety of IORT for BrMs.