Bone mineral density (BMD) is only one of several bone strength determinants affected by osteoporosis therapies. Trabecular Bone Score (TBS), a gray-level texture index determined from lumbar spine (LS) dual-X-ray absorptiometry scans, is an indirect measure of bone microarchitecture independent of and complementary to BMD and clinical risk factors. In the Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH), monthly subcutaneous romosozumab 210 mg for 12 mo followed by 24-mo open-label weekly oral alendronate 70 mg (romosozumab-to-alendronate) significantly reduced fracture risk compared to 36-mo alendronate alone in postmenopausal women with osteoporosis and prior fracture. This analysis evaluated tissue thickness-adjusted TBS (TBSTT) in a subgroup of patients from ARCH who had post-hoc TBS measurements at baseline and at least one post-baseline visit at months 12, 24, and 36. Baseline characteristics were similar between romosozumab-to-alendronate (n = 190) and alendronate alone (n = 188). Romosozumab led to significantly greater gains in TBSTT vs alendronate at month 12 (least squares mean difference, 3.6%), with greater gains maintained after transition to alendronate and persisting at months 24 (2.9%) and 36 (2.3%; all p<.001). Romosozumab-to-alendronate increased the percentage of individual patients with "normal" TBSTT from 28.9% at baseline to 48.1%, 43.9%, and 45.4% at months 12, 24, and 36, respectively, and decreased the percentage of individual patients with degraded TBSTT from 52.6% to 33.3%, 36.0%, and 33.5%, respectively (all p<.001). A similar but smaller trend was observed with alendronate alone from baseline through month 36 (p ≤.012). Changes in TBSTT and LS BMD were largely unrelated from baseline to month 12 (romosozumab-to-alendronate, r2 = 0.065; alendronate alone, r2 = 0.021) and month 36 (r2 = 0.058; r2 = 0.057, respectively). In postmenopausal women with osteoporosis and prior fracture, 12-mo romosozumab followed by 24-mo alendronate significantly improved bone microarchitecture estimated by TBSTT more than 36-mo alendronate alone.