Effective transition programs are essential for adolescents and young adults with sickle cell disease (SCD), yet their long-term impact remains unexplored. The St. Jude SCD Transition Program provides structured transition interventions, such as disease education, personal health record (PHR) communication training, transition skills-building, academic guidance, and early adult care introduction for patients aged 12 to 25 years. This 13-year retrospective cohort study evaluated program effectiveness on first adult visit attendance, successful transfer to adult care, adult ambulatory and acute care use, and health-related quality of life (HRQOL). Among 638 patients, 74.5% attended their first adult visit and 40.0% successfully transferred to adult care (2 visits within the first year after transfer). Increased participation in nearly all transition interventions was associated with first adult visit attendance, and all interventions were associated with successful transfer. In-person SCD education and early introduction to adult care were independently associated with first adult visit attendance, whereas in-person SCD education and PHR training were independently associated with successful transfer. A predictive model incorporating intervention exposure and demographics yielded an area under the curve of 0.81 for attendance at the first adult visit (95% confidence interval, 0.75-0.88; sensitivity 0.76, specificity 0.70). PHR training was associated with adult ambulatory use up to 3 years after transfer and improved early adulthood HRQOL. No interventions were associated with acute care use. Transition interventions that improve disease literacy, communication, and care transfer processes are linked to better transition outcomes and HRQOL, though sustained adult care engagement remains low. Future research is needed to promote adult care engagement.