Head-up tilt testing is a reliable diagnostic tool for patients with recurrent unexplained syncope. It has also been used to assess the drug efficacy for the treatment of patients with syncope. The objective of this study was to assess the efficacy of verapamil compared with metoprolol in a randomized crossover design for patients with syncope and a positive tilt test response. Twenty-eight patients with a positive head-up tilt test were randomized to receive either metoprolol or verapamil; the test was repeated after 7 days of therapy. Of the 15 patients initially given metoprolol, 2 (13.3%) did not respond; both were crossed over to verapamil, to which they remained unresponsive. Of the 13 patients who initially received verapamil, 8 (61%) did not respond; after crossing over to metoprolol therapy, 1 remained unresponsive. Overall, 20 of 23 patients receiving metoprolol had negative results on repeat tilt testing, whereas only 5 of 15 patients receiving verapamil had negative results (p < 0.001). In conclusion, the results of this study suggest that verapamil is considerably less efficacious than metoprolol in managing neurocardiogenic syncope.