This study evaluated a possible placebo effect by pacemaker implantation. The study design was a 3-month multicenter, double-blind, randomized cross-over study to compare the effects of atrioventricular (AV) synchronous pacing with an optimal AV delay to inactive pacing in patients with obstructive hypertrophic cardiomyopathy (HC). Quality of life and left ventricular (LV) outflow tract obstruction were evaluated after the first study period in 40 patients assigned to inactive pacing. Data were compared with the corresponding results among the 41 subjects assigned to a first study period of active pacing. During inactive pacing, there was a significant improvement in perceived chest pain, dyspnea, and palpitations. Moreover, LV outflow tract gradient decreased from 71 +/- 32 mm Hg to 52 +/- 34 mm Hg (p = 0.04). In patients assigned to active pacing the reduction of the gradient was significantly more pronounced (70 +/- 24 mm Hg to 33 +/- 27 mm Hg; p <0.0001). The difference in gradient reduction between the groups was highly significant (p <0.00001). In the group assigned to active pacing there was also significant improvement in perceived symptoms as well as in alertness, the ability to be self-autonomous, and strenuous physical exercise. The improvements in the latter were significantly greater in those paced actively compared with patients paced inactively, whereas the changes in perceived symptoms did not differ between groups. In conclusion, pacemaker implantation had a placebo effect on objective and subjective parameters in this group of patients with obstructive HC.