A randomized trial was conducted to test the effectiveness of couple-based HIV counseling and testing (CB-HIV-CT) and women-only relationship-focused HIV counseling and testing (WRF-HIV-CT) in reducing HIV risk compared to the National Institute on Drug Abuse HIV-CT standard intervention. Substance using HIV-negative women and their primary heterosexual partner (N = 330 couples) were randomized to 1 of the 3 interventions. Follow-up assessments measuring HIV risk behaviors and other relevant variables were conducted at 3- and 9-months postintervention. Repeated measures generalized linear mixed model analysis was used to assess treatment effects. A significant reduction in HIV risk was observed over the 9-month assessment in the CB-HIV-CT group compared to that of the control group (b = -0.51, t[527] = -3.20, P = 0.002) and compared to that of the WRF-HIV-CT group (b = -0.34, t[527] = -2.07, P = 0.04), but no significant difference was observed between WRF-HIV-CT and controls (b = -0.17, t[527] = -1.09, P = 0.28). A brief couple-based HIV counseling and testing intervention designed to address both drug-related and sexual risk behaviors among substance using women and their primary male partners was shown to be more effective at reducing overall HIV risk compared to a standard HIV-CT intervention in an urban setting.