The enrollment process determines the study sample and external validity of clinical trial results; however, few reports describe the process and outcome of screening efforts for smoking cessation studies among adolescents. We describe and evaluate a screening protocol to enroll adolescent smokers for a randomized clinical trial of nicotine replacement therapy. Adolescent smokers obtained the recruitment call-in number (1-800-NO-SMOKE) via media and other advertisements. Trained recruitment staff collected information using an internally developed, targeted telephone screening interview, which was used to determine pre-eligibility for the clinical trial. Correlates of qualification and of study enrollment were determined. Among 1,347 adolescents screened, 329 (24.4%) were eligible to participate in the trial. Light smoking (39.1%) and lack of parental support (14.8%) were the biggest contributors to ineligibility. Eligible adolescents were more likely to be female (66.9% vs. 58.2%, p = .0052) and more likely to be European American (63.5% vs. 52.2%, p = .0003). The higher rates of ineligibility for African Americans and boys were partly explained by lower scores on the Fagerström Test for Nicotine Dependence. Of those eligible to participate in the trial, 159 (48.3%) enrolled. Results underscore the need for screening instruments that are measurement-invariant across ethnicities and gender, and for enrollment strategies that maximize inclusion of eligible participants.