To measure changes in health-related quality of life and breast-related symptoms after reduction mammaplasty in adolescents. In this longitudinal cohort study, we administered the Short-Form 36v2 (SF-36), Rosenberg Self-Esteem Scale (RSES), Breast-Related Symptoms Questionnaire (BRSQ), and Eating Attitudes Test-26 to 102 adolescents with macromastia and 84 female controls, aged 12 to 21 years. Patients with macromastia completed surveys preoperatively and after reduction mammaplasty at 6 months and 1, 3, and 5 years. Controls completed baseline and follow-up surveys at the same intervals. Patients with macromastia demonstrated significant score improvements postoperatively from baseline on the RSES, BRSQ, and in 7 out of 8 SF-36 domains: physical functioning, role-physical, bodily pain, vitality, social functioning, role-emotional, mental health (P < .001, all). By the 6-month follow-up visit, postoperative subjects scored similarly to or more favorably than controls on the RSES, BRSQ, Eating Attitudes Test-26 , and SF-36; these benefits persisted for at least 5 years and were not significantly affected by BMI category or age. Reduction mammaplasty was significantly associated with improvements in health-related quality of life and breast-related symptoms of adolescent patients, with measureable improvements in physical and psychosocial well-being evident by 6 months postoperatively and still demonstrable after 5-years. These results largely do not vary by BMI category or age. Patients and providers should be aware of the potential positive impact that reduction mammaplasty can provide adolescents with symptomatic macromastia. Historic concerns regarding age and BMI category at the time of surgery should be reconsidered.