To determine the relative contribution of psychological and neuropsychological (NP) variables to the prediction of patterns of coping with disease-related stressors and satisfaction with their coping efforts, 56 patients with multiple sclerosis (MS) were administered the Ways of Coping Checklist, the Symptom Checklist-90-Revised, and a battery of NP tests chosen for their sensitivity to MS. Higher levels of psychological distress were associated with greater use of emotion-focused coping strategies and reduced perceived effectiveness of the coping strategies employed. Psychological distress was not related to the use of problem-focused strategies and NP variables did not predict coping style or effectiveness. MS patients who display heightened psychological distress may be good candidates for psychotherapeutic interventions aimed at improving perceived coping effectiveness. © 1999 John Wiley & Sons, Inc. J Clin Psychol 55: 21–26, 1999.