BACKGROUND: Vigorous left ventricular (LV) contraction with progressive ventricular emptying during orthostatic stress may induce hyper-responsiveness of cardiac mechanoreceptor and vasovagal syncope (VVS). We hypothesized that intracardiac volume reserve estimated by the left atrial (LA) volume index (LAVI) plays an important role in the mechanism of VVS. METHODS: A total of 234 patients (115 male, 44짹18 years) who underwent head-up tilt test (HTT) and transthoracic echocardiography for unexplained syncope were consecutively enrolled. Patients with a positive HTT result (HTT+; n=152) were compared with those with negative HTT response (HTT-; n=82). RESULTS: 1. Compared to HTT- patients, HTT+ patients were younger (41짹17 vs. 48짹17 years, p=0.005), included a higher number of females (56% vs. 50%, p=0.009) and showed higher basal heart rate (67짹12 vs. 63짹11 bpm, p=0.047). 2. LAVI (20짹5 vs. 26짹13 mL/m2, p<0.001), LV end-diastolic dimension (47.4짹3.7 vs. 49.0짹4.1 mm, p=0.015), and the proportion of LV hypertrophy (13% vs. 24%, p=0.027) were smaller and early diastolic mitral annulus velocity were higher (9.7짹3.0 vs. 8.5짹2.6 cm/s, p=0.004) in HTT+ patients than those in HTT- group. 3. LAVI was the only independent predictor of HTT induced VVS (OR 0.884, CI 0.781-0.989, p=0.049), and had a linear correlation with time to syncope during HTT (r=0.39, p=0.034). In addition, patients with LAVI���36 mL/m2 did not faint during HTT. CONCLUSION: Small LA volume is an independent predictor of HTT-induced VVS. Limited intracardiac volume reserve might play an important role in the mechanism of VVS.