BACKGROUND Approximately 3% to 10% of patients with syncope experience episodes while driving. The aim of our study was to identify their clinical and pathophysiological features, estimate the incidence of recurrence, and correlate these characteristics with recurrence. METHODS We prospectively studied 40 patients who experienced syncope while driving and 50 subjects who experienced syncope in other situations. All cases underwent upright tilt test (UTT), with simultaneous ECG and beat-to-beat blood pressure recordings, to analyze heart rate variability, total peripheral resistance (TPR), and stroke volume (SV). RESULTS Patients who experienced syncope while driving suffered more frequently from hypertension (40% vs 20%) and vasodepressive reactions during the UTT (52% vs 26%). Moreover, these patients had increased heart rates (p=0.007) and lower SVs (p=0.006) during a positive UTT. TPR rose immediately before symptoms appeared only in patients who suffered from nondriving syncope (p=0.006). During a mean follow-up of 1793±573 days, 8 syncopic patients while driving had recurrences (20%) but never while driving. They were older, experienced more episodes of syncope, and had a higher incidence of vasodepressive reactions during UTT. CONCLUSIONS Our study confirms a good prognosis for patients who experience syncope while driving, and indicates that more accurate risk stratification is needed in subjects aged over 50 years, who have had more than 4 episodes of loss of consciousness and vasodepressive reactions during UTT.