© 2020, The International Urogynecological Association. Introduction and hypothesis: Limited data exist comparing different surgical approaches in women with advanced vaginal prolapse. This study compared 2-year surgical outcomes of uterosacral ligament suspension (ULS) and sacrospinous ligament fixation (SSLF) in women with advanced prolapse (stage III–IV) and stress urinary incontinence. Methods: This was a secondary analysis of a multicenter 2 × 2 factorial randomized trial comparing (1) ULS versus SSLF and (2) behavioral therapy with pelvic floor muscle training versus usual care. Of 374 subjects, 117/188 (62.7%) in the ULS and 113/186 (60.7%) in the SSLF group had advanced prolapse. Two-year surgical success was defined by the absence of (1) apical descent ' 1/3 into the vaginal canal, (2) anterior/posterior wall descent beyond the hymen, (3) bothersome bulge symptoms, and (4) retreatment for prolapse. Secondary outcomes included individual success outcome components, symptom severity measured by the Pelvic Organ Prolapse Distress Inventory, and adverse events. Outcomes were also compared in women with advanced prolapse versus stage II prolapse. Results: Success did not differ between groups (ULS: 58.2% [57/117] versus SSLF: 58.5% [55/113], aOR 1.0 [0.5–1.8]). No differences were detected in individual success components (p ' 0.05 for all components). Prolapse symptom severity scores improved in both interventions with no intergroup differences (p = 0.82). Serious adverse events did not differ (ULS: 19.7% versus SSLF: 16.8%, aOR 1.2 [0.6–2.4]). Success was lower in women with advanced prolapse compared with stage II (58.3% versus 73.2%, aOR 0.5 [0.3–0.9]), with no retreatment in stage II. Conclusions: Surgical success, symptom severity, and overall serious adverse events did not differ between ULS and SSLF in women with advanced prolapse. ClinicalTrials.gov Identifier: NCT01166373.