OBJECTIVES: Recent advances in image-guided brachytherapy have allowed for treatment volume reduction in the treatment of prostate cancer, with the aim to optimize disease control and reduce toxicities. This systematic review reports on the efficacy and safety of focal brachytherapy for treatment of patients with localized prostate cancer. METHODS: Medline, Embase, Web of Science, and Cochrane were searched from inception to July 2023. Studies were included if they reported on focal brachytherapy, and described either dosimetry or clinical outcomes in the monotherapy or salvage setting. Meta-analysis was conducted to estimate biochemical control (BC) at 12-60 months. The review protocol was registered on PROSPERO (CRD42022320921). RESULTS: Twenty-six studies reporting on 1492 patients were included in this review. Fourteen studies reported on monotherapy, 10 on salvage, and two on boost. The majority of studies used MRI and/or biopsy or PET for target identification, and MRI fusion and transrectal ultrasound (TRUS) for image guidance technique. BC for monotherapy was 97% (95% CI: 86%-99%) at 24 months and 82% (95% CI: 65%-92%) at 60 months. BC for salvage was 67% (95% CI: 62%-72%) at 24 months and 35% (95% CI: 17%-58%) at 60 months. Low rates of toxicity were reported across studies. CONCLUSIONS: Focal brachytherapy has promising efficacy and safety profiles. Future studies may compare focal brachytherapy to whole-gland treatments, to investigate relative efficacy and safety. ADVANCES IN KNOWLEDGE: In well-selected patients, partial or focal brachytherapy represents an evidence-based option with acceptable BC rates and a favourable toxicity profile.