Objective: This cross-sectional study analyzed associations between and determinants for health-related quality of life (HRQoL), fatigue, and societal participation in polytrauma patients. Summary of background data: More polytrauma patients survive their injuries, often resulting in long-term disabilities. HRQoL is therefore an important outcome of trauma care. Fatigue and societal participation may be related to HRQoL. Also, their relation to severe injuries has not been studied to date. Methods: A total of 283 polytrauma patients (injury severity score 16) admitted to the Dutch level 1 Trauma Centre West were analyzed. HRQoL was measured by the physical component summary (PCS) and mental component summary (MCS) scores of the SF-36, fatigue by the multidimensional fatigue inventory, and societal participation by the Utrecht scale for evaluation of rehabilitation-participation. Age, sex, comorbidity, injury pattern, injury severity, and time since trauma were analyzed as potential determinants. Results: A total of 122 patients (43%) responded after a median follow-up of 15 (range, 10–23) months after polytrauma; 44% reported reduced physical health (PCS, 45) and 47% reported reduced mental health (MCS, 45). HRQoL was highly correlated with all fatigue and participation subscales. Severe head injury was associated with worse mental health. Female patients reported more general and mental fatigue and were less satisfied with their ability to perform daily activities. Patients with pre-existing comorbidity experienced worse physical health, more fatigue, and reduced societal participation. Conclusions: One to 2 years after trauma, polytrauma patients report reduced HRQoL, which is associated with more fatigue and reduced societal participation. Trauma rehabilitation strategies should focus on early recognition of reduced HRQoL, fatigue, and societal participation and facilitate early intervention to improve these outcomes.@en