ImportanceTransfascial (TF) mesh fixation in open retromuscular ventral hernia repair (RVHR) has been advocated to reduce hernia recurrence. However, TF sutures may cause increased pain, and, to date, the purported advantages have never been objectively measured.ObjectiveTo determine whether abandonment of TF mesh fixation would result in a noninferior hernia recurrence rate at 1 year compared with TF mesh fixation in open RVHR.Design, Setting, and ParticipantsIn this prospective, registry-based, double-blinded, noninferiority, parallel-group, randomized clinical trial, a total of 325 patients with a ventral hernia defect width of 20 cm or less with fascial closure were enrolled at a single center from November 29, 2019, to September 24, 2021. Follow-up was completed December 18, 2022.InterventionsEligible patients were randomized to mesh fixation with percutaneous TF sutures or no mesh fixation with sham incisions.Main Outcome and MeasuresThe primary outcome was to determine whether no TF suture fixation was noninferior to TF suture fixation for open RVHR with regard to recurrence at 1 year. A 10% noninferior margin was set. The secondary outcomes were postoperative pain and quality of life.ResultsA total of 325 adults (185 women [56.9%]; median age, 33 [IQR, 50-67] years) with similar baseline characteristics were randomized; 269 patients (82.8%) were followed up at 1 year. Median hernia width was similar in the TF fixation and no fixation groups (15.0 [IQR, 12.0-17.0] cm for both). Hernia recurrence rates at 1 year were similar between the groups (TF fixation, 12 of 162 [7.4%]; no fixation, 15 of 163 [9.2%]; P = .70). Recurrence-adjusted risk difference was found to be −0.02 (95% CI, −0.07 to 0.04). There were no differences in immediate postoperative pain or quality of life.Conclusions and RelevanceThe absence of TF suture fixation was noninferior to TF suture fixation for open RVHR with synthetic mesh. Transfascial fixation for open RVRH can be safely abandoned in this population.Trial RegistrationClinicalTrials.gov Identifier: NCT03938688