BACKGROUND: Several mechanisms may be involved in the trigger of syncope in patients with hypertrophic cardiomyopathy (HCM), including hemodynamic collapses that might be related to an autonomic imbalance. OBJECTIVE: To evaluate and compare the autonomic function of patients presenting HCM with unexplained syncope (US) to those without syncope. METHODS: Thirty-seven patients were included, 16 with US and 21 without syncope. Their autonomic function was assessed by spontaneous and phenylephrine induced baroreflex sensitivity (BRS), by heart rate variability (HRV) in time domain during 24-hour Holter and in frequency domain (spectral analysis), both in supine position and at 70 masculine head-up tilt (HUT). RESULTS: The spontaneous BRS was similar in both groups (16,46 +/- 12,99 vs. 18,31 +/- 9,88 ms/mmHg, p = 0,464), as was phenylephrine-induced BRS (18,33 +/- 9,31 vs. 15,83 +/- 15,48 ms/mmHg, p = 0,521). No differences were observed in SDNN (137,69 +/- 36,62 vs . 145,95 +/- 38,07 ms, p=0,389). The group presenting syncope had a significantly lower RMSSD (24,88+/-10,03 vs. 35,58 +/- 16,43 ms, p = 0,042) and a tendency to lower pNN50 (4,51 +/- 3,78 vs . 8,83 +/- 7,98%, p =0,085) and lower values of the high frequency component of HRV spectral analysis at rest (637,59+/-1.295,53 vs. 782,65+/-1.264,14ms2, p=0,075). No significant difference was observed in response to HUT (p = 0,053). HUT sensitivity, specificity and accuracy in identifying the etiology of US in HCM patients were 6%, 66% and 40%, respectively. CONCLUSIONS: A lower parasympathetic tone was observed in HCM patients with US, but the clinical relevance of this finding remains unclear. HUT is not a valuable tool for evaluating the origin of syncope in these patients, mainly because of its poor specificity.