Introduction and hypothesis: EndoFast Reliant™ system is a novel technology for pelvic organ prolapse (POP) repair that attaches mesh directly with metal fasteners. Methods: This was a prospective multicenter study in 20 women who underwent vaginal POP repair to evaluate safety and efficacy. The patients were followed for 12 months, using POP-Q measures, questionnaires on symptoms (PFDI), and sexual function (FSFI). Results: No intraoperative complications occurred. Prolapse has been anatomically resolved (< stage 2) in 85% at 1-year follow-up (17/20 patients). Pelvic Floor Distress Inventory (PFDI) scores showed significant improvement for 1 year in symptoms related to prolapse (4.1-0.7, p < 0.001) and bladder (1.4-0.7, p = 0.06) but not to rectum. Female Sexual Function Index (FSFI) scores did not change significantly. One case of mesh exposure was found (5%) and treated conservatively. No migration of fasteners was observed on X-ray. Conclusions: The EndoFast Reliant™ system was found safe and efficacious. Future studies are needed to evaluate its advantages over techniques using trocars.