ObjectiveAlthough single-fraction high-dose-rate brachytherapy (SFHDR) for localized prostate cancer has been tried in clinical trials, relevant medical evidence is currently lacking. It is necessary to systematically analyze the safety and efficacy of SFHDR.MethodsComprehensive and systematic searches for eligible studies were performed in PubMed, Embase, and the Cochrane Library databases. The primary endpoints included safety and efficacy, represented by toxic effects and biochemical recurrence-free survival (bRFS), respectively. The proportion rates were used as the effect measure for each study and were presented with corresponding 95% confidence intervals (CI) and related 95% prediction interval (PI). Restricted maximum-likelihood estimator (REML) and the Hartung–Knapp method were used in the meta-analysis.ResultsTwenty-five studies met the inclusion criteria for quantitative analysis, including 1440 patients. The median age of patients was 66.9 years old (62–73 years old) and the median follow-up was 47.5 months (12–75 months). The estimates of cumulative occurrence for severe gastrointestinal (GI) and genitourinary (GU) toxic effects were 0.1% (95% CI 0–0.2%) and 0.4% (95% CI 0–1.2%), and for grade 2 toxic effects were 1.6% (95% CI 0.1–4.7%) and 17.1% (95% CI 5.4–33.5%), respectively. The estimate of 3‑year bRFS was 87.5% (95% CI 84.4–90.3%) and 71.0% (95% CI 63.0–78.3%) for 5‑year bRFS. The pooled bRFS rates for low-risk patients were 99.0% (95% CI 85.2–100.0%) at 3 years and 80.9% (95% CI 75.4–85.9%) at 5 years, and the risk group was found to be statistically correlated with bRFS (3-year bRFS,P< 0.01; 5‑year bRFS,P= 0.04).ConclusionSFHDR is associated with favorable tolerability and suboptimal clinical benefit in patients with localized prostate cancer. Ongoing and planned high-quality prospective studies are necessary to verify its safety and efficacy.Supplementary InformationThe online version of this article (10.1007/s00066-023-02063-z) contains supplementary material, which is available to authorized users.