BACKGROUND: Gender-affirming surgery is a quickly expanding field. However, it is facing a shortage of specialized surgeons for a population exceeding 1.4 million individuals. Many studies comparing outcomes between cisgender and transgender patients fail to describe the technical differences of the operation. Breast augmentation in the transgender female patient involves important anatomical, technical, and clinical features that differ from the cisgender female. In this study, we aimed to describe and compare these characteristics between these 2 groups to better inform the new generation of gender-affirming surgeons. METHODS: A retrospective cohort study of patients who underwent primary breast augmentation between 2009 and 2019 at a specialized tertiary center for transgender care was performed. Mastopexy, secondary augmentation, and reconstructive procedures were excluded. Demographic, operative, and clinical data were collected from medical records. All patients had a minimum of 1 year of follow-up after the initial surgery. Bivariate analysis was performed. RESULTS: A total of 250 cisgender females and 153 transgender females were included. The transgender group showed higher rates of smoking ( P < 0.0001), immunosuppression ( P < 0.0001), obesity ( P < 0.0001), mental health disorders ( P < 0.0001), and hypertension ( P = 0.002). Median base width ( P < 0.0001), sternal notch to nipple distance ( P < 0.0001), and implant size (500 mL [interquartile range, 425-600 mL] vs 350 mL [interquartile range, 325-385 mL]; P < 0.0001) were larger in transgender patients. Transgender patients also demonstrated a stronger correlation between implant size and body surface area ( r = 0.71, P < 0.0001). Readmission, reoperation, and complication rates were similar between the groups; however, transgender females had a higher incidence of surgical site infections (3.9% vs 0.4%, P < 0.013). Capsular contracture was the most common complication and indication for reoperation in both groups. CONCLUSIONS: There are important anatomical, clinical, and technical differences between reconstructive gender-affirming breast augmentation in transgender female patients and cosmetic breast augmentation in the cisgender female. The gender-affirming surgeon must know these differences to provide the best quality of care and help patients achieve better congruence between their gender identity and body image.