The long-term stability of combined orthopedic and orthodontic therapies remains a critical determinant of treatment success, yet comparative multicenter data examining skeletal, dentofacial, and functional outcomes across diverse treatment protocols are limited. This multicenter clinical study evaluated long-term stability outcomes in 487 adolescent patients treated with combined orthopedic-orthodontic protocols across five academic centers, with minimum 5-year follow-up post-treatment. The aim was to quantify skeletal and dentofacial relapse patterns, identify risk factors for instability, and establish evidence-based frameworks for retention and relapse prevention. Methodological frameworks included standardized cephalometric analysis at pretreatment, post-treatment, and long-term follow-up intervals, supplemented by cone-beam computed tomography in selected cases and functional outcome assessment using validated indices. Key findings demonstrate that Class II correction with functional appliances followed by fixed orthodontics maintained 78-85% of skeletal mandibular advancement at long-term follow-up, with greater stability observed when treatment coincided with peak growth velocity (CVMS 3-4). Class III maxillary protraction with expansion followed by fixed appliances maintained 70-80% of maxillary advancement, with bone-anchored protraction demonstrating superior stability (85-90%) at 5-year follow-up. Transverse expansion maintained 80-90% of skeletal expansion when retention protocols were followed, with hybrid expansion showing enhanced stability in older adolescents. Relapse risk factors included unfavorable growth patterns (hyperdivergent Class II, continued mandibular growth in Class III), post-treatment growth exceeding 2 years, inadequate retention duration, and poor compliance with retention protocols. Functional outcomes demonstrated maintained improvements in masticatory function and airway dimensions correlating with skeletal stability. Implementation analysis revealed that standardized retention protocols, risk-stratified follow-up schedules, and interdisciplinary coordination optimize long-term outcomes. The study concludes that combined orthopedic-orthodontic therapies achieve clinically acceptable long-term stability when treatment timing, mechanical protocols, and retention strategies are appropriately matched to individual patient characteristics. Translational implications include development of risk-prediction models, personalized retention protocols, and multicenter registry frameworks for ongoing outcome surveillance.