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Objective: The aim of the present study was to identify disease parameters, defensive styles and ego strength measurements associated with various forms of psychiatric complications in patients with multiple sclerosis (MS). Methods: Seventy-nine patients with MS participated in the study and 158 healthy subjects matched for age and sex served as controls. A wide range of clinical information was collected and the following self-report instruments were used: General Health Questionnaire, Symptom Distress Check List, Defense Style Questionnaire, MMPI Ego Strength Scale and Hostility and Direction of Hostility Questionnaire. Results: The odds of being assessed with a psychiatric diagnosis upon interview were 6.7 times greater among patients compared to controls and 9.3 times greater among patients with recent-onset MS compared to patients with long-term disease. Psychiatric complications of MS were closely associated with age of the disease onset and the degree of disability due to MS. Additionally, higher rates of introverted hostility, adoption of maladaptive ego defenses and weakened ego strength were also closely associated with several forms of psychological distress, especially depressive symptoms. Conclusions: MS patients experience elevated symptoms of psychological distress, especially depressive symptoms, which are most closely associated with disease parameters. However, the crucial role of various personality traits such as ego defenses and hostility features in the psychiatric symptom formation also appear to contribute to the development of depressive symptoms. Clinicians involved in the clinical management of patients with MS should identify and modify treatment if these specific personality markers that indicate the exhaustion of the patient's resources to cope with the physical and psychological stress of the illness are present.