It is unknown if the head-upright tilt test in patients who receive isoproterenol and nitroglycerin can identify different populations with vasovagal syncope. The aim of this study was to compare the positive or negative responses to passive tilt between isoproterenol- and nitroglycerin-sensitized upright tilt. Ninety-six patients referred for unexplained recurrent syncope underwent passive tilt (45 minutes at 70° angle), which was then systematically followed, within the same session and in a random order, by a 20-minute tilt at a 70° angle after administration of nitroglycerin (NTG-tilt) and 10-minute tilt at a 70° angle with a continuous infusion of isoproterenol (ISO-tilt). NTG-tilt led to significantly more positive responses than passive tilt or ISO-tilt (55% vs 34% vs 42%, respectively). In the subgroup of patients with a positive response during passive tilt, the percentage of positive responses with NTG-tilt was significantly higher than with ISO-tilt (94% vs 67%). The agreement between NTG-tilt and ISO-tilt was very weak (Kappa coefficient 0.06). In the subgroup of patients with a negative response during passive tilt, the percentage of positive responses between NTG-tilt and ISO-tilt was similar (35% vs 29%). The agreement between NTG-tilt and ISO-tilt was good (Kappa coefficient 0.34). NTG-tilt led to a higher number of positive responses than ISO-tilt, especially when passive tilt outcome was positive. These 2 pharmacologic agents may identify 2 different subpopulations of patients because of their specific pharmacologic actions.