Purpose: To determine whether illicit drug users recruited through respondent-driven sampling (RDS) and targeted street outreach (TSO) differ by comparing two samples recruited concurrently with respect to sample selection and potential recruitment biases.Methods: Two hundred seventeen (217) heroin, crack, and cocaine users aged 18–40 years were recruited through TSO in New York City (2006–2009). Forty-six RDS seeds were recruited similarly and concurrently, yielding a maximum of 14 recruitment waves and 357 peer recruits. Baseline questionnaires ascertained sociodemographic, drug use, and drug network characteristics. Descriptive statistics and log-binomial regression were used to compare RDS and TSO samples.Results: RDS recruits were more likely to be male (prevalence ratio [PR]:1.28), Hispanic (PR:1.45), black (PR: 1.58), older (PR: 1.02), homeless (PR: 1.19), and crack users (PR: 1.37). RDS recruited fewer injectors (PR:0.35) and heroin users (PR:0.74). Among injectors, RDS recruits injected less frequently (PR:0.77) and were less likely to use Needle Exchange Programs (PR:0.35).Conclusion: These data suggest that RDS and TSO strategies reach different subgroups of drug users. Understanding the differing capabilities of each recruitment strategy will enable researchers and public health practitioners to select an appropriate recruitment tool for future research and public health practice.