The primary objective was to assess the effect of the route of closure of the vaginal cuff on the incidence of vaginal cuff dehiscence (VCD) in laparoscopic hysterectomy (LH). The secondary objective was to assess patient- and surgical-risk factors associated with VCD, rate of perioperative complications by route of closure, and impact of surgeon volume on complications. Retrospective chart review with case-control component. Tertiary care center (main hospital and regional hospitals). A total of 1278 women underwent LH or robot-assisted hysterectomy in 2016, and met the inclusion criteria. Independently, 26 cases of VCD were identified from 2009 through 2016. A retrospective comparison of patients with vaginal cuff closure and laparoscopic cuff closure (LCC) undergoing LH or robot-assisted hysterectomy in 2016. Patients with VCD from 2009 through 2016 (n = 26) were matched by route of cuff closure to the next 7 patients who underwent hysterectomies (n = 182), who became controls. In 2016, there were 9 cases of VCD (0.70%). There was no significant difference in VCD between LCC (8/989; 0.81%) and vaginal cuff closure (1/289; 0.35%; p = .41). Seven VCD cases were performed by high-volume surgeons (>30 hysterectomies per year) who were more likely to perform LCC and use barbed suture. There were no significant differences in the rates of perioperative complications or surgeon volume between routes of cuff closure. The case-control patients differed in smoking status (p = .010) and history of prior laparotomy (p = .017). Logistic regression showed that increasing age (odds ratio 0.95; 95% confidence interval, 0.91-0.99) and increasing body mass index (odds ratio 0.98; 95% confidence interval, 0.83-0.97) were protective for VCD. VCD is a rare but serious complication of LH. Despite previous studies, we did not find a significant difference in VCD or intra- and perioperative complications by route of cuff closure or surgeon volume. Given the lack of evidence favoring one route of cuff closure, we recommend that, to optimize patient outcomes, surgeons employ the closure technique that they are best accustomed to.