We examined effects of the Early Risers “Skills for Success” early-age-targeted prevention program on serious conduct problems following 5 years of continuous intervention and one year of follow-up. We also examined if intervention effects on proximally-targeted variables found after 3 years mediated intervention effects on conduct problems found after 6 years. Participants included 151 at-risk children (106 males and 45 females) followed from first through sixth-grade, from 23 semi-rural schools in Minnesota. After 6 years, program children showed fewer oppositional defiant disorder (ODD) symptoms than control children. Program children did not significantly differ from controls on number of conduct disorder (CD) symptoms, DSM-IV diagnoses of ODD and CD, or drug use involvement. Results of the mediation analysis indicated that fewer ODD symptoms among program youth after 6 years were partially mediated by social skills and effective discipline. The study provides support for the early-starter model of conduct problems development that provides the framework for the Early Risers intervention. The study’s implications for prevention and limitations are discussed.