Background: Reduction mammaplasty effectively alleviates symptoms and restores quality of life. However, operating on adolescents remains controversial, partly because of fear of potential postoperative breast growth. This cross-sectional study provides surgeons with a method to predict the optimal timing, or biological “sweet spot,” for reduction mammaplasty to minimize the risk of breast regrowth in adolescents. Methods: The authors reviewed the medical records of women aged 12 to 21 years who underwent reduction mammaplasty from 2007 to 2019. Collected data included symptomology, perioperative details, and postoperative outcomes. Results: Four hundred eighty-one subjects were included in analyses and were, on average, 11.9 years old at first menses (menarche) and 17.9 years old at surgery. Six percent of subjects experienced postoperative breast growth. Breast size appears to stabilize considerably later in obese adolescents compared to healthy-weight and overweight patients, and breast growth in obese macromastia patients may not end until 9 years after menarche. Operating on obese women before this time point increased the likelihood of glandular breast regrowth by almost 120 percent (OR, 1.18; 95 percent CI, 1.11 to 1.26). Surgery performed less than 3 years after menarche, the commonly regarded end of puberty, increased the likelihood of glandular regrowth by over 700 percent in healthy-weight and overweight subjects (OR, 7.43; 95 percent CI, 1.37 to 40.41). Conclusions: Findings suggest that reduction mammaplasty age restrictions imposed by care providers and third-party payors may be arbitrary. Surgical readiness should be determined on an individual basis incorporating the patient’s biological and psychological maturity, obesity status, potential for postoperative benefit, and risk tolerance for postoperative breast growth. Clinical Question/Level of Evidence: Risk, III.