Syncope is a common condition. Tilt testing with sublingual nitroglycerin (TT-TNT) provides a test with good specificity and positivity rate in young and old patients. Its use in hypertensive patients with unexplained syncope has not been validated. The aims of this study were to evaluate the positivity rate, specificity and tolerability of TT-TNT in hypertensive patients with unexplained syncope. Five hundred and ten subjects (mean age 55 years) were enrolled, 388 patients with unexplained syncope (73 hypertensive and 315 normotensive) and 122 controls (59 hypertensive and 63 normotensive). All subjects underwent TT-TNT. The responses were classified as positive, negative or exaggerated (aspecific). In hypertensive patients, the usual hypotensive therapy was taken on the day of the test. In hypertensive controls, the positive responses were higher than in normotensives (19% vs 6%, P<0.001). The overall specificity was 81% in hypertensives and 94% in normotensives. The positivity rate was significantly lower in hypertensives (55% vs 72%, P<0.03). There was no significant difference between young patients and patients >65 years. TT was well tolerated, and no serious side effects occurred. TT potentiated with TNT has a lower positivity rate and specificity in hypertensive than in normotensive patients with syncope.