Adults at increased risk for hepatitis B virus (HBV) infection are recommended to receive vaccination. We conducted a cost utility analysis to evaluate approaches for implementing that recommendation in selected high-risk settings: community outreach events with a large proportion of immigrants, syringe service programs, substance use treatment centres, sexually transmitted infection (STI) clinics, tuberculosis (TB) clinics and jails. We utilized a decision tree framework with a Markov disease progression model to compare quality adjusted life-years and cost in 2021 United States dollars from four strategies: a 3-dose vaccination regimen with prevaccination screening and testing (PVST; baseline comparison); PVST at the initial encounter followed by a 2-dose series (Intervention 1); PVST with the first dose of a 2-dose vaccination series at the initial encounter (Intervention 2); and a 2-dose vaccination series without PVST (Intervention 3). In all settings, Intervention 1 resulted in worse health outcomes compared with the baseline strategy. Intervention 2 averted incident chronic HBV infections in all settings (range -9.4% in TB clinics, -14.8% in syringe service programs) and was a cost-saving approach in settings with higher risk of infection (i.e. jails, -$266 per person; syringe service programs, -$597; substance use treatment centres, -$130). Providing a 2-dose vaccination series without any screening (Intervention 3) averted incident HBV infections and was cost-saving in all settings but resulted in more HBV-related deaths in settings with higher HBV prevalence. These results demonstrate a 2-dose vaccine series is a cost-effective approach in these high-impact settings, even if prevaccination testing is not possible.