We aimed to assess the psychiatric profile and prognostic value of psychiatric disorders (PDs) in patients presenting with unexplained syncope. Forty patients with recurrent unexplained syncope referred for head-up tilt testing were compared with age- and sex-matched patients free of known chronic PDs referred for arrhythmia. All patients underwent a semistandardized psychiatry questionnaire (Mini-International Neuropsychiatric Interview) to assess their profile. Additional stress coping was performed to study adaptational processes to stressful situations. After tilt testing and psychiatric evaluation, a drug-free follow-up was performed in patients with syncope. Of the 80 patients who referred to the psychiatric interview, 40 had evidence of at least 1 psychiatric disorder. They were 26 patients (65%) in the syncope group and 14 patients (35%) in the control group (p = 0.01). Detailed analysis revealed a more frequent subprofile of anxiety and panic disorders in patients with syncope than in controls (30% vs 12% and 20% vs 10%, respectively), whereas the subprofile of depression was similar in both groups. Moreover, those with syncope were more likely to have a high anxiety index (25 +/- 5 vs 22 +/- 4, p = 0.004), and were more prone to avoidance-oriented coping strategies when experiencing undesirable life events than controls. Considering syncope patients, no difference could be found between the 25 with a positive tilt test and the 15 with a negative tilt test with respect to the number of syncopal episodes and psychiatric profile. After a 3-year drug-free follow-up, 15 patients (37.5%) had at least 1 recurrent syncope. The recurrence rate was similar in patients with positive and negative head-up tilt test results (9 of 25 vs 6 of 15, respectively). In contrast, the syncopal recurrence rate was higher in patients who fulfilled criteria for affective disorders (13 of 26 vs 2 of 14, 95% confidence interval 1.09 to 2.55, relative risk 1.7, p = 0.04). Thus, patients with recurrent unexplained syncope are more anxious and are more prone to panic disorders and avoidance-oriented coping strategies than control patients with arrhythmia. The presence of a psychiatric disorder is associated with an increased risk of recurrence. The outcome of such patients may be improved with recognition and treatment of PDs.