OBJECTIVE: To assess the safety of vascular closure devices in living-donor nephrectomy (LDN), as staplers and non-transfixion techniques (polymer locking and metal clips) are the methods employed to secure the renal vessels during laparoscopic and robotic LDN, but the use of clips has come into question since the United States Food and Drug Administration and manufacturers issued a contraindication. METHODS: A systematic review and meta-analysis were conducted to assess the safety of vascular closure devices (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42022364349). The PubMed, Scopus, the Excerpta Medica dataBASE (EMBASE), and the Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) databases were searched in September 2022. For comparative and non-comparative studies, incidence estimates and odds ratios (ORs), respectively, for the main variables regarding safety of vascular closure devices were pooled by using random effects meta-analyses. Quality assessment of the included comparative studies was conducted using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. RESULTS: Of the 863 articles obtained, data were retrieved from 44 studies, which included 42 902 patients. In non-comparative studies, the pooled estimate rates for device failure, severe haemorrhage rate, conversion to open surgery, and mortality were similar for both clips and staplers. Regarding the meta-analyses for comparative studies (three studies), there were no significant differences between the two groups for the severe haemorrhage rate (OR 0.57, 95% confidence interval [CI] 0.18-1.75; P = 0.33), conversion to open surgery (OR 0.35, 95% CI 0.08-1.54; P = 0.16), or death rate (OR 3.64, 95% CI 0.47-28.45; P = 0.22). Based on weak evidence, device failure was lower in the polymer clip group (OR 0.41, 95% CI 0.23-0.75; P = 0.00). CONCLUSIONS: This study has confirmed that there is no evidence for the superiority of any vascular closure device in terms of safety in LDN. Standardised recommendations for vascular control in this context should be carefully designed and prospectively evaluated.