Hepatitis B virus (HBV) vaccination for PWH is an important prevention intervention that decreases risk of developing chronic liver disease and related complications such as hepatocellular carcinoma. Among PWH, serologic response to primary vaccination with older HBV vaccines (e.g., Engerix-B, Recombivax HB) varies notably and has led to multiple vaccination studies and strategies. The purpose of this retrospective cohort study was to examine seroprotection rates (SPR) and predictors among adults without current HBV seroprotection (defined as anti-HBs < 10 mIU/mL) followed at a single quaternary care center HIV clinic who received at least one dose of Heplisav-B. Heplisav-B was approved in 2017 as a 2-dose vaccine and contains an immunostimulatory adjuvant; of note, PWH were not included in the trials which led to initial FDA approval. Among 64 PWH engaged in care at the study location, 63 received a complete 2-dose series, and 81% demonstrated post-vaccination seroprotection overall (defined as anti-HBs titers ≥ 10 mIU/mL); 63% achieved anti-HBs titers ≥ 100 mIU/mL. Seroprotection rate was 86% in patients without significant non-HIV immunosuppression, e.g. decompensated cirrhosis, solid organ transplantation, metastatic cancer, active chemotherapy, or asplenia. Seroprotection rates among PWH who underwent primary vaccination with Heplisav-B versus among PWH without a history of seroprotection after receiving older HBV vaccines (and subsequently received Heplisav-B) were 79% and 84%, respectively. Higher current and nadir CD4 cell counts were associated with seroprotection (p < 0.001 for both). There were no differences in pre- and post-immunization HIV viral load measurements; 90% of patients were virologically suppressed on ART.