INTRODUCTION AND HYPOTHESIS:This study assessed the safety and efficacy of vaginal extraperitoneal uterosacral ligament suspension (VEULS) with anterior overlay mesh versus sacrocolpopexy (SCP) for posthysterectomy vault prolapse. METHODS:This was a multicenter randomized trial of women with posthysterectomy vault prolapse stage >2 according to the Pelvic Organ Prolapse Quantification (POP-Q) system. Primary outcome was a composite of no vaginal bulge symptoms, no anatomical recurrence in the anterior or apical compartment at or beyond the hymenal ring, and no surgical retreatment for prolapse 12 months postsurgery. Secondary outcomes were peri- and postoperative complications, changes in prolapse, and urogenital and sexual symptoms at 12, 24, and 48 months based on the Pelvic Floor Distress Inventory (PFDI)-20. RESULTS:Between 2006 and 2011, 82 eligible women were randomized: 39 received VEULS and 43 received SCP. Primary composite outcome at 12 months for success was 41% for VEULS and 65% for SCP [odds ratio (OR 2.68, p = 0.03)]. Perioperative complications were more common in the SCP group. C-point was higher for SCP (-6.0 VEULS vs -8.0 SCP, p = 0.005) and total vaginal length (TVL) was longer for SCP (8.0 VEULS vs 9.0 SCP, p = 0.05). Cumulative mesh exposure rate at 4 years was similar between the uterosacral [4/39 (10.3%)] and sacrocolpopexy [4/43 (9.3%)] groups, bearing in mind that not all patients were examined at 4 years. Subjective outcomes derived from three domains of the PFDI-20 were similar at 12, 24, 48 months. Postoperative Pelvic Organ Prolapse Distress Inventory (POPDI) score improved similarly for both groups at all timepoints, with the minimally important difference of at least 21 reached for both groups. CONCLUSIONS:Composite outcome of success was better for SCP at 12 months, but subjective outcomes for prolapse at all timepoints over 4 years for VEULS and SCP were not significantly different.