BACKGROUND: The combined oral contraceptive pill, containing both estrogen and progestin, is commonly prescribed to adolescents for numerous health benefits. However, there is concern among patients and providers that its use may exacerbate breast growth. This retrospective, case-control study examined the association between combined oral contraceptive pill use and macromastia-related breast hypertrophy and symptoms in adolescents. METHODS: A total of 378 patients undergoing reduction mammaplasty between the ages of 12 and 21 years were assessed for baseline and postoperative breast symptoms and combined oral contraceptive pill use. In addition, the medical records of 378 female controls of the same age range were retrospectively reviewed. RESULTS: Although a lower proportion of the macromastia cohort used any hormonal contraception compared to controls (37.8 percent versus 64.8 percent; OR, 0.33; 95 percent CI, 0.24 to 0.44; p < 0.001), they were more often prescribed combined oral contraceptive pills (82.5 percent versus 52.7 percent; OR, 1.93; 95 percent CI, 1.29 to 2.68; p < 0.001). Participants with macromastia who used combined oral contraceptive pills had a smaller median normalized amount of breast tissue resected during reduction mammaplasty than those who never used hormonal contraception (639.5 g/m 2 versus 735.9 g/m 2 ; p = 0.003). Combined oral contraceptive pills were not associated with breast-related symptoms or clinical impairment, or postoperative breast growth ( p > 0.05 for all). CONCLUSIONS: Combined oral contraceptive pill use during adolescence may be associated with developing less severe breast hypertrophy. Combined oral contraceptive pills do not appear to exacerbate macromastia-related symptoms or impact postoperative growth in young women following reduction mammaplasty. Although additional research is needed, providers are encouraged to consider combined oral contraceptive pills for their patients with macromastia when indicated and appropriate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.