The USPHS/IDSA guidelines for Prevention of Opportunistic Infections in Persons with human immunodeficiency virus (HIV) recommends that all susceptible HIV+ patients at increased risk for hepatitis A virus (HAV) or with chronic liver disease, be vaccinated against HAV. Immune response to HAV vaccine has not been well studied in HIV+ patients. In particular, there is little information in the literature regarding the effect and relationship of the CD4 count and the immune response in HIV patients. A retrospective analysis of HIV+ patients who received HAV vaccine was performed, and the antibody response to HAV (anti-HAV) measured. Univariate and multivariate analyses were performed to determine predictors of response to vaccine administration. Of the 503 patients evaluated, 138 patients completed their HAV vaccination series and 48% of them had postvaccine anti-HAV positive results (responders). There was no difference in age, race, antiretroviral therapy use, or hepatitis C virus exposure between responders and nonresponders. In univariate analysis, responders were more likely to be female (40.3%vs 21.1%, P = 0.01), have a higher CD4 count at vaccine (508.6 cells/mm3 vs 344.3 cells/mm3, P = 0.001) and marginally lower viral load at vaccine (2.65 log copies vs 2.94 log copies, P = 0.07). Multivariate analysis showed that female gender and higher CD4 count at vaccine were independent predictors of response to vaccine. Forty-eight per cent of our HIV+ patients responded to HAV vaccine administration. This is much lower than reported rates of 100% in HIV-negative patients. Female gender and CD4 count at vaccine, but not CD4 nadir, predicted response to vaccine.