Aims: Presented herein are the post Week 48 through Week 96 resistance analyses for Phase 3 studies evaluating tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF). Methods: Patients were randomized 2:1. HBV pol/RT population or deep sequencing was conducted for patients with viremia at Week 96 or at early discontinuation post Week 48. Deep sequencing was conducted for patients with HBV DNA >159 IU/mL and sequence changes at the consensus sequence level are reported. Phenotypic analysis was performed for Virologic breakthrough (VB) patients who were adherent to study drug, patients with conserved site substitutions, or for polymorphic substitutions emergent in >1 patient. Results: TAF and TDF were treated in 866 and 432 patients, respectively. A similar percentage of patients in the arms qualified for sequence analysis. In the TAF arm, 87 (10.5%) patients qualified: 31 had no sequence change from baseline, 15 were unable to sequence (UTS), 32 had polymorphic site substitutions, and 9 had conserved site substitutions. In the TDF arm, 45 (10.9%) patients qualified: 26 had no sequence change, 6 were UTS, 11 had polymorphic site substitutions, and 2 had conserved site substitutions. Each detected conserved site substitution other than rtA181T was observed in one patient. The rtA181T substitution in 2 patients, 1 from each arm, was not associated with increasing plasma HBV DNA levels. At Week 96, a small percentage of patients experienced VB, and VB was often associated with nonadherence. 27 patients qualified for phenotypic analysis and no patient isolates tested showed a reduction in susceptibility to TAF or tenofovir, respectively. Conclusions: The proportion of patients analyzed and the HBV sequence changes observed were similar between patients in the TAF and TDF arms. Most substitutions occurred at polymorphic positions and no substitutions associated with resistance to TAF were detected through 96 weeks of treatment.