We describe challenges in the 6-year longitudinal cluster randomized controlled trial (CRCT) of Positive Action (PA), a social–emotional and character development (SECD) program, conducted in 14 low-income, urban Chicago Public Schools. Challenges pertained to logistics of study planning (school recruitment, retention of schools during the trial, consent rates, assessment of student outcomes, and confidentiality), study design (randomization of a small number of schools), fidelity (implementation of PA and control condition activities), and evaluation (restricted range of outcomes, measurement invariance, statistical power, student mobility, and moderators of program effects). Strategies used to address the challenges within each of these areas are discussed. Incorporation of lessons learned from this study may help to improve future evaluations of longitudinal CRCTs, especially those that involve evaluation of school-based interventions for minority populations and urban areas.