The aim of this study was to assess the impact of psychological features in the choice of coping strategies in multiple sclerosis (MS) patients, and their influence on quality of life (QoL). One hundred four patients (72 women, age 45.3 +/- 10.9 years, disease duration 17.9 +/- 13.2 years, Expanded Disability Status Scale 2.8 +/- 2.0) were assessed through the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Eysenck Personality Questionnaire, the Coping Orientation for Problem Experiences-New Italian version and the MSQoL-54. MS patients were less likely to use problem-focused strategies, whereas avoiding strategies were adopted more frequently. The use of positive strategies positively influenced both mental and overall QoL. Depression had a negative impact on all QoL domains and anxiety on mental domains. These data point out the importance of a comprehensive assessment of MS patients. Orienting therapeutic interventions, to oppose depression and anxiety and to favour more appropriate coping strategies can improve the patients' QoL.