ABSTRACT Objective Vaginal cuff dehiscence, a severe and potentially detrimental complication, has significantly increased after the introduction of endoscopic hysterectomy. The aim of this systematic review and meta-analysis of the available literature was to identify the incidence of, and possible strategies to prevent, this complication after total laparoscopic hysterectomy and total robotic hysterectomy. Data Sources PubMed, ClinicalTrials.gov, Scopus, and Web of Science databases were systematically queried to identify all articles reporting either laparoscopic or robot-assisted hysterectomies for benign indications in which vaginal dehiscence was reported as an outcome. Reference lists of the identified studies were manually searched. Only papers written in English were considered. Methods of Study Selection The Population, Intervention, Comparison, and Outcome framework for the review included (1) population of interest: women who underwent conventional and robot-assisted laparoscopic hysterectomy; (2) interventions: possible methods to prevent vaginal dehiscence; (3) comparison: experimental strategies vs standard treatment or alternative strategy for each item of intervention; and (4) outcome: rate of vaginal dehiscence. Series of subtotal hysterectomies and radical hysterectomies in addition to reports that combined both benign and malignant cases were excluded. The meta-analysis was performed using RevMan version 5.4.1 (Cochrane Training, London, United Kingdom). Two independent reviewers identified all reports comparing 2 or more possible strategies to prevent vaginal dehiscence. Tabulation, Integration, and Results A total of 460 articles were identified. Of these, 20 (6 randomized, 2 prospective, and 12 retrospective) studies were included in this review for a total of 19 392 patients. The incidence of vaginal dehiscence after total laparoscopic hysterectomy ranged between 0.64% and 1.35%. Robotic hysterectomy was associated with a risk of vaginal dehiscence of approximately 1.64%. No study compared early vs delayed resumption of coital activity nor analyzed the role of training in laparoscopic suturing. No study specifically assessed the impact of electrosurgery on the risk of vaginal dehiscence in endoscopic hysterectomies for benign indications. Double-layer and reinforced sutures did not decrease the risk of dehiscence. Barbed sutures reduced the risk of separation compared with nonbarbed closure (0.4% [4/1108] vs 2% [22/1097]; odds ratio [OR] 0.25; 95% confidence interval [CI], 0.11–0.57). However, these data came mainly from retrospective series. Excluding studies on the use of self-anchoring sutures during robotic hysterectomy, there was no significant difference in the risk of dehiscence between barbed and nonbarbed sutures (0.5% [4/890] vs 1.4% [181/776]; OR 0.38; 95% CI, 0.13–1.10). Transvaginal suture of the vault at the end of an endoscopic hysterectomy seemed to increase the risk of dehiscence when compared with laparoscopic closure (2.3% [23/1002] vs 1.16% [11/944]; OR 1.97; 95% CI, 1.00–3.88). Conclusion There is a paucity of high-quality papers evaluating vaginal dehiscence and possible prevention strategies in the current literature. Only 2 effective strategies have been identified in reducing the risk for this complication: the use of barbed sutures and the adoption of a laparoscopic approach to close the vaginal cuff. When restricting the analysis only to laparoscopic cases, the use of barbed sutures does not protect against vaginal cuff separation.