Background: It is largely unknown how quality of life (QoL) changes following accidental injuries. Equally, the mechanisms underlying such changes have not yet been identified in detail. This study of injured accident survivors aimed to: (1) detect a model of change which best explains the observed course of QoL, and (2) identify potential predictor variables. Methods: 323 injured accident survivors were interviewed within 2 weeks of the trauma, and followed up at 6 and 12 months. Latent trajectory modeling was used to analyze the fit of three potential trajectories regarding the observed course of general QoL as measured by the Questions on Life Satisfaction questionnaire. Results: The trajectory model adopting a negative square-root change fitted the observed data best, meaning that shortly after the accident, general QoL decreased strongly with diminishing negative changes occurring later on. Early and prolonged QoL impairment was largely attributable to the initial level of posttraumatic stress as measured by the Clinician-Administered PTSD Scale. To a lesser extent, depressive symptoms also predicted change in subjective QoL, while injury severity showed no direct effect; rather, its impact on QoL was mediated by initial posttraumatic stress. By contrast, reduced occupational functioning was attributable to injury severity rather than psychopathology. Conclusions: When treating injured accident survivors, clinicians should consider symptoms of posttraumatic stress and comorbid depression in order to prevent or mitigate negative changes in QoL.