Respondent-driven sampling (RDS) has been promoted as a superior method in recruiting hard-to-reach and hidden populations. Although its application has expanded enormously, there remains a need for empirical data evaluating the performance of RDS in different settings. This study describes the application of RDS to recruit a community sample (N = 396) of young adults (18–23 years old) into a natural history study of non-medical pharmaceutical opioid use. Since recruitment targeted non-dependent pharmaceutical opioid users, and applied other eligibility restrictions, several modifications had to be made to make RDS work with this narrowly defined target population. RDS recruitment was less efficient than expected, and produced greater numbers of African American recruits than anticipated. Although the sampling quota was met, sample analysis revealed a lack of equilibrium in terms of ethnic composition and very strong in-group recruitment tendencies among White and African American respondents. This study contributes potentially helpful insights into the strengths and limitations of using RDS which may benefit future studies.