Estimates of HIV incidence rates among high-risk heterosexuals (HRH) in the United States have been limited to heterosexual subgroups like prison inmates and commercial sex workers. In this analysis, we estimate incidence with detuned assay testing among a group of HRH defined through a multidimensional sampling strategy and recruited through respondent-driven sampling. Incidence was 3.31% per year (95% confidence interval = 1.43 to 6.47) overall and 2.59% per year (95% confidence interval = 0.84 to 6.06) among participants with no lifetime history of drug injection or male-to-male sex. This study design is suggested as an efficient method for recruiting HRH for cohort studies and behavioral interventions.