BACKGROUND: Gender confirming primary breast augmentation is becoming more common. The purpose of this study was to compare the demographic and anatomical differences in cis-female and trans-female populations. METHODS: This was a retrospective analysis of trans-female patients and cis-female patients undergoing primary breast augmentation at a single institution. Analysis included patient demographics and preoperative chest measurements including sternal notch to nipple distance (SSN), breast width (BW), nipple to inframammary fold distance (N-IMF), and nipple to midline distance (N-M). Continuous variables were compared using independent tests, and discrete variables were compared using Pearson's χ tests. RESULTS: Eighty-two trans-female and 188 cis-female patients undergoing primary breast augmentation were included. Trans-female patients were older (40.37 versus 34.07), more likely to have psychological comorbidities (50% versus 12.23%), and had a higher body mass index, 27.46 kg/m versus 22.88 kg/m ( = 1.91E-07), than cis-female patients. Cis-female patients most commonly had an ectomorph body habitus (52% versus 26%), whereas trans-female patients most commonly had an endomorph body habitus (40% versus 7%). Pseudoptosis or ptosis was more commonly seen in cis-female patients ( = 0.0056). There were significant differences in preoperative breast measurements including sternal notch to nipple distance, BW, and N-M between groups, but not in N-IMF. The ratio of BW/N-IMF was statistically significant ( = 2.65E-07 on right), indicating that the similarity in N-IMF distance did not adjust for the difference in BW. CONCLUSIONS: The trans-female and cis-female populations seeking primary breast augmentation have significant demographic and anatomical differences. This has implications for surgical decision-making and planning to optimize outcomes for trans-female patients.