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Background: Reduction mammaplasty is increasingly common in younger patients with macromastia. Unfortunately, a recent surge in mental health disorders has been documented in this population. It is unknown how mental health disorders affect patients undergoing reduction mammaplasty. This study examines the impact of concurrent mental health conditions on health-related quality of life outcomes after reduction mammaplasty. Methods: A prospective cohort study was performed on patients aged 12–21 years undergoing reduction mammaplasty. Patients were assigned to unaffected or affected (baseline mental health condition) cohorts based on psychological history. Patients completed the Short-form-36, Rosenberg Self-esteem Scale, Eating Attitudes Test 26, and Breast-related Symptoms Questionnaire at baseline and postoperatively. Results: A total of 250 patients were included (81 affected and 169 unaffected). Mean age at surgery was 17.9 ± 2.0 and 18.1 ± 1.8 years for affected and unaffected patients, respectively. Anxiety (n = 59, 23.6%) and depression (n = 38, 15.2%) were the most prevalent conditions. Affected patients were outscored by controls at baseline and postoperatively in most measures. However, significant score improvements were also reported in the affected cohort. In fact, the magnitude of score improvements observed in both cohorts were similar (P > 0.05, all). Conclusions: Baseline mental health conditions are common in young patients presenting for reduction mammaplasty. After surgery, health-related quality of life in affected patients remains below unaffected peers; however, significant and similar gains are achieved. We advise providers to recommend mental health treatment to affected patients, but not preclude otherwise appropriate candidates from surgery.

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