Purpose: Early medical treatment for transgender adolescents should contribute to healthy psychological development, including the development of positive self-perception. However, at present, there are no longitudinal studies that have examined whether current treatment approaches meet this expectation. Therefore, the aim of this single-arm retrospective study was to examine transgender adolescents' self-perception changes over the course of irreversible medical gender-affirming treatment. Methods: The total study sample consisted of 70 adolescents (49 trans men and 21 trans women). Self-perception was assessed before the start of gender-affirming hormone treatment (mean age = 14.65, standard deviation (SD) = 2.08) and at least 6 months after gender-affirming surgeries (mean age = 20.70, SD = 1.49) by Self-Perception Profile for Adolescents (SPPA). The SPPA is a self-report measure that examines self-perception on seven different domains: Scholastic competence, social acceptance, athletic competence, physical appearance, behavioral conduct, close friendship, and global self-worth. Multilevel modeling (random intercepts model) was conducted to determine the effect of time for all domains of self-perception. Results: It was found that the domains of physical appearance and global self-worth improved significantly over the course of treatment. No domain worsened significantly over the course of treatment. The domains of scholastic competence, social acceptance, athletic competence, and close friendship remained stable over time. Conclusion: This study provides the first suggestive evidence that irreversible gender-affirming treatment for adolescents could contribute to the development of a more positive self-perception.