Alarmingly high HIV prevalence rates among African American men who have sex with men (AAMSM) require the development of effective prevention interventions. In this study of AAMSM conducted in two cities, we explored similarities and differences between HIV-positive and HIV-negative AAMSM on sociodemographic variables, HIV-related risk behaviors, and attitudinal constructs. Differences emerged in several major life areas: (1) poverty, employment, and use of mental health services, (2) sexual risk behaviors, and (3) self-identification with gay identity and culture. With regard to sociodemographic indicators, HIV-positive AAMSM were doing worse than HIV-negative AAMSM in that they were more likely to be disabled, to be living below the poverty level, and accessing mental health services. With regard to risk behaviors and partner characteristics, HIV-positive AAMSM were acting more responsibly than their HIV-negative counterparts, as they were more likely to have used a condom the last time they had sex. In addition, when compared to their HIV-negative counterparts, HIV-positive AAMSM were more likely to have either no casual partners at all or main or casual partners who were HIV-positive, thus preventing new HIV transmission by partnering with other HIV-positive men. Attitudinally, HIV-positive men were more accepting of their sexual attractions to men and were more likely to identify as gay than their HIV-negative peers. Although causality cannot be determined, the findings of this study can be used to strengthen HIV prevention efforts by improving the selection of targeted behaviors and prevention messages for HIV-positive and HIV-negative AAMSM.