Patients were assigned to one of two vaccine schedules to assess the feasibility of vaccinating a sexually transmitted disease clinic population against hepatitis B virus. Of 1386 patients entering an inner-city clinic between June and July 1990, 611 (44%) accepted a first dose of vaccine. Twenty-one percent of all susceptible patients received at least two doses of vaccine. Annualizing these findings shows that an ongoing program could prevent 636 hepatitis B virus infections per year. Although a significant proportion of sexually transmitted disease clinic patients can be successfully vaccinated, strategies for preventing hepatitis B virus infections in this high-risk population must consider patient behavior as well as vaccine efficacy.