There is a paucity of empirical reports that quantitatively assess the success of recruitment strategies in randomized clinical trials (RCTs) using sampling units other than the individual. As innovations in HIV and sexually transmitted infection (STI) preventive intervention protocols and targets of change evolve, there is a need to examine the efficacy of attendant adaptations to recruitment protocols and strategies in the enrollment of study participants. This article examines factors related to enrollment of women and their main, male sexual partners in an RCT of a relationship-based HIV/STI preventive intervention conducted from 1997 to 2001. Among eligible participants (N = 388), findings indicate that race/ethnicity, employment status, marital status, and language preference were significantly associated with enrollment among eligible, potential participants. Additionally, being HIV-positive and having a past or current STI were significantly associated with enrollment. These findings underscore the need to ensure sufficient representation of all risk groups in RCTs, especially those testing innovative HIV/STI preventive intervention approaches or using novel enrollment strategies.