This study examined the utility of a stress and coping model of adjustment to multiple sclerosis (MS) caregiving. A total of 89 MS caregivers and their care recipients completed self-administered scales at Time 1 and 12 months later, Time 2 (n 5 51). Predictors included care recipient disability and distress, caregiver gender, social support, appraisal (threat, control and challenge) and problem-and emotion-focused coping strategies. Adjustment outcomes were Times 1 and 2 depression, global distress and caregiving impact. Almost one-third of the caregivers reported clinically signi cant levels of psychological distress. Results from hierarchical regression analyses on the cross-sectional data indicated that after controlling for the effects of caregiver gender, better Time 1 adjustment was related to less care recipient disability and distress, higher social support, lower threat appraisals and less reliance on emotion-focused coping and, unexpectedly, problem-focused coping. These relations were supported by correlations performed on the longitudinal data. Findings support the utility of a stress and coping model of adaptation to caregiving in MS.