Background. Medical gender-affirming interventions (GAI) are important in the transition process of many trans persons. The aim of this study was to examine the associations between GAI and quality of life (QoL) of transitioned trans individuals. Methods. 143 trans persons were recruited from a multicenter outpatient Swiss population as well as a web-based survey. The QoL was assessed using the Short Form (36) Health Survey questionnaire (SF-36). Depressive symptoms were examined using the Short Form of the Center for Epidemiologic Studies-Depression Scale (ADS-K). Multiple interferential analyses and a regression analysis were performed. Results. Both transfeminine and transmasculine individuals reported a lower QoL compared to the general population. Within the trans group, nonbinary individuals showed the lowest QoL scores and significantly more depressive symptoms. A detailed analysis identified sociodemographic and transition-specific influencing factors. Conclusions. Medical GAI are associated with better mental wellbeing but even after successful medical transition, trans people remain a population at risk for low QoL and mental health, and the nonbinary group shows the greatest vulnerability.