Recruitment challenges for treatment trials of adolescents with substance use disorder (SUD) and co-occurring depression (COD) have not been reported. The objective is to examine whether recruitment and engagement during the pretreatment assessment phase differ between adolescents in a SUD-COD versus SUD-only treatment study. A similar recruitment approach compared five-stage progressions in the pretreatment phase between a SUD-only (n = 252) and SUD-COD (n = 212) study. We examined the "gradient" of recruitment and retention along four stages after referral/inquiries; (a) screening for eligibility by phone, (b) meeting eligibility in an interview, (c) completion of baseline assessment, and (d) participation in the first psychotherapy session of each study. Compared to SUD-only, the retention of adolescents with SUD-COD was significantly poorer from referral/inquiry to all subsequent stages. In particular, the odds ratio and 95% confidence interval from referral/inquiry to screening for eligibility by phone, meeting eligibility in an interview, completion of baseline assessment, and participation in the first psychotherapy session were all less than one. Male attrition rates were slightly higher than females but were not statistically significant. A high proportion of referred adolescents did not meet the study criteria. This indicates a need to examine (1) potential strategies for overcoming recruitment challenges in adolescents and their engagement in the pretreatment phase for studies of COD and (2) baseline variables for predictors and moderators for adequately powered studies. This is the first study to assess recruitment challenges for adolescents with COD.