Background <p>To investigate the cumulative health burden and complex challenges to adjustment following road traffic injuries (RTIs), this study examined multiple environmental, personal, and health-related factors and outcomes over 12&#xa0;months in a comprehensive and holistic way, comparing these outcomes between injured and non-injured controls.</p> Methods <p>A longitudinal controlled cohort study was conducted with two groups: adults with mild to moderate RTIs and non-injured controls. Assessments occurred at 1, 3, 6, and 12&#xa0;months post-injury. The study involved 120 RTI participants and 112 controls. Data on physiological, psychological, cognitive, and social factors were collected and analyzed using the World Health Organization International Classification of Functioning, Disability, and Health (ICF) framework. The ICF Components—Impairments in Body Functions and Structures, Limitations in Activity, Restrictions to Participation, Environmental and Personal Contextual Factors—were used to link and categorize data and compare outcomes, allowing comprehensive evaluation of RTI-related burden and adjustment challenges.</p> Results <p>The RTI group exhibited significantly worse outcomes across all measured ICF Components, including higher pain, fatigue, psychological distress, and cognitive impairment. Despite some improvements over time, the RTI group continued to experience elevated symptoms, functional limitations, and restricted participation compared to controls at 12&#xa0;months.</p> Conclusions <p>RTIs lead to sustained, multidimensional challenges to adjustment, emphasizing the need for early, comprehensive, and ongoing interventions for at least 1-year post-injury. These findings highlight the importance of evaluating multiple biopsychosocial factors and adopting a holistic framework to fully understand recovery patterns. Addressing these factors simultaneously across multiple systems is essential to improve recovery outcomes.</p> Trial registration <p>ACTRN12616001445460.</p>