This study examined the use of a stress and coping model of adjustment to multiple sclerosis (MS). A total of 122 MS patients were interviewed and completed self-administered scales at Time 1 and 12 months later, Time 2 (n = 96). Predictors included stressful life events, illness (duration, severity, and disability), social support, appraisal (threat and control/challenge), and coping (problem focused and emotion [wishful thinking, self-blame, and avoidance] focused). Adjustment outcomes were Time 2 depression, global distress, social adjustment, and subjective health status. Results from hierarchical regression analyses indicated that after controlling for the effects of Time-1 adjustment, better Time-2 adjustment was related to less disability, greater reliance on problem-focused coping, and less reliance on emotion-focused coping. There was limited support for the stress buffering effects of coping and social support. Findings offer some support for the use of a stress and coping model of adaptation to MS.