Aims: Compared with TDF, smaller declines in bone mineral density (BMD) were demonstrated with TAF vs. TDF over 48 weeks. Presented here are bone safety results at Week 96. Methods: In two Phase 3 studies, 1301 patients were randomized (2:1) to receive TAF 25 mg QD or TDF 300 mg QD. Dual energy X-ray absorptiometry (DXA) scans were evaluated for mean percent change from baseline and by the proportion with >3% declines in hip and spine BMD. BMD changes were also assessed in the subset of patients at higher risk for bone loss (females, advanced age [≥ 50 y], Asian race, eGFR <90 mL/min). Serum markers of bone resorption (CTX) and formation (osteocalcin, bone-specific alkaline phosphatase, P1NP) were also assessed serially. Results: Patients with TAF experienced lesser declines in hip and spine BMD over 96 weeks(Table, p< 0.001). A higher proportion of subjects treated with TDF also experienced >3% declines in hip and spine BMD compared with TAF-treated patients (Table, p < 0.0001). Greater declines in BMD were seen in patients with >1 risk factor for bone loss at baseline; however, in comparison to TDF, the proportion with >3% declines in hip and spine BMD were lower in the TAF group (p<0.0001 for all) and were less impacted by the presence of multiple risk factors (Table, p< 0.005 for all). By multivariate analysis baseline predictors for >3% decline in hip or spine BMD at Week 96 were: treatment with TDF, female gender, and older age. The smaller changes in BMD seen with TAF were associated with minimal changes in markers of bone turnover compared with TDF. Conclusions: Through 96 weeks, TAF was associated with had less impact on BMD and bone parameters compared to TDF. The magnitude of these differences was most pronounced in those at higher risk for bone loss.