Objective: To determine unique demographic, medical, perceived health, and handicap predictors of life satisfaction 2 years after spinal cord injury (SCI), as well as the predictors of change in life satisfaction from year 1 to year 2. Design: Prospective predictive study performed by using longitudinal data from 18 Spinal Cord Injury Model Systems. Setting: University physical medicine and rehabilitation department. Participants: Adults with traumatic onset SCI (N = 940) evaluated at 1 and 2 years' postinjury. Interventions: Not applicable. Main Outcome Measures: Satisfaction with Life Scale (SWLS) 2 years post-SCI. Predictor variables: demographic characteristics, impairment and disability classifications, and 1 year post-SCI measures of life satisfaction (SWLS), medical complications, self-perceived health (Medical Outcomes Study 12-Item Short-Form Health Survey), and extent of handicap (Craig Handicap Assessment and Reporting Technique). Results: The factors uniquely associated with an increased risk of lower self-reported life satisfaction at year 2 post-SCI included being male and unemployed, with poor perceived health, decreased mobility, and decreased social integration. After controlling for year 1 estimates of life satisfaction (ie, examining change in life satisfaction), only mobility and perceived health were uniquely related to life satisfaction 2 years post-SCI. Conclusion: Mobility and perceived health appear to be the consistent predictors of life satisfaction at year 2 post-SCI, as well as change in satisfaction from year 1 to year 2. Because both factors are amenable to change, they are reasonable targets of intervention programs. Identifying specific mechanisms of perceived health and mobility associated with life satisfaction should be an important area of continued research. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation.