OBJECTIVES: Puberty suppression (PS) is a cornerstone of treatment in youth experiencing gender dysphoria. In this study, we aim to inform prescribing professionals on the long-term effects of PS treatment on the development of sex characteristics and surgical implications. METHODS: Participants received PS according to the Endocrine Society guideline at Tanner 2 or higher. Data were collected from adolescents who received PS between 2006 and 2013 and from untreated transgender controls. Data collection pre- and post-PS and before surgery included physical examination and surgical information. RESULTS: In total, 300 individuals (184 transgender men and 116 transgender women) were included. Of these, 43 individuals started PS treatment at Tanner 2/3, 157 at Tanner 4/5, and 100 used no PS (controls). Breast development was significantly less in transgender men who started PS at Tanner 2/3 compared with those who started at Tanner 4/5 and controls. Mastectomy was more frequently omitted or less invasive after PS. In transgender women, the mean penile length was significantly shorter in the PS groups compared with controls (by 4.8 cm [Tanner 2/3] and 2.1 cm [Tanner 4/5]). As a result, the likelihood of undergoing intestinal vaginoplasty was increased (odds ratio = 84 [Tanner 2/3]; odds ratio = 9.8 [Tanner 4/5]). CONCLUSIONS: PS reduces the development of sex characteristics in transgender adolescents. As a result, transgender men may not need to undergo mastectomy, whereas transgender women may require an alternative to penile inversion vaginoplasty. These surgical implications should inform decision-making when initiating PS.