Aims - To describe health-related quality of life (HRQL) 2years after moderate-to-severe traumatic brain injury (TBI) and to assess predictors of HRQL. Materials and methods - A prospective cohort study of 91 patients, aged 16-55years, admitted with moderate-to-severe TBI to a trauma referral centre between 2005 and 2007, with follow-up at 1 and 2years. Mean age was 31.1 (SD=11.3) years, and 77% were men. Injury severity was evaluated by the Glasgow Coma Scale (GCS), head CT scan (using a modified Marshall Classification), Injury Severity Score (ISS) and post-traumatic amnesia (PTA). The Functional Independence Measure (FIM), Community Integration Questionnaire (CIQ), Beck Depression Inventory (BDI) and Medical Outcomes 36-item Short Form Health Survey (SF-36) were administered at follow-up visits. The main outcome measures were the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36. Results - HRQL appears to be relatively stable between 1 and 2years after injury. In the multivariate linear regression, younger age (=-0.20, P=0.032), more severe TBI (=0.28, P=0.016), more severe overall trauma (=0.22, P=0.026), higher levels of community integration (=0.36, P=0.019) and higher positive change in PCS scores from 1 to 2years (=0.41, P<0.001) predicted better self-reported physical health 2years post-TBI. Lower scores for depression (=-0.70, P<0.001) and a higher positive change in MCS scores (=0.62, P<0.001) predicted better self-reported mental health. Conclusions -Future interventions should focus on aspects related to HRQL that are more easily modified, such as physical functioning, home and social integration, productivity, and mental and emotional status.