Purpose Trauma is still a major burden in global public health. In the past, multiple pieces of trauma research focused on mortality as an outcome parameter. The purpose of this study is to evaluate the global health-related quality of life (HRQoL) of adolescents after multiple trauma. Methods We conducted a multicenter prospective registry-based study on patients aged 16-24 years who sustained a multiple trauma (ISS>16). Data acquisition was based on the trauma registry of the German Trauma Society (DGU). Additionally, the global HRQoL was measured using the EQ-5D score at 6, 12, and 24 months post trauma. Results We identified 77 patients meeting the inclusion criteria. There were 65 male (84%) and 12 female (16%) patients. The average age at time of injury was 20.27 years (±2.34). The mean ISS was 26.4 (±10.58). Six months post multiple trauma, we found an EQ-5D index score of 0.85. The score improved after 12 and 24 months to 0.87. There was no significant correlation between the ISS of any body region and the EQ-5D index value at 6, 12, or 24 months. Conclusions We found a limited HRQoL measured by an EQ-5D index score six months post multiple trauma. There was an improvement in HRQoL from 6 to 12 months and a stable condition between 12 and 24 months after trauma. Compared to normal values of healthy subjects, this still suggests an impairment of HRQoL after multiple trauma.