The purpose of this study was to evaluate the efficacy, safety, and tolerance of pindolol as initial therapy for vasovagal syncope. Head-up tilt table testing (HUT) was performed on 192 patients for syncope or near-syncope of unknown cause. Forty-four (23%) patients had a positive HUT for vasovagal syncope, and 28 (64%) received oral pindolol as initial therapy. Three patients were lost to follow-up; of the remaining 25 patients (mean age 60 +/- 22 years), 15 were women, 14 had syncope, and 11 had near-syncope. At 14 +/- 6 months' follow-up, 16 (64%) patients were without recurrence or side effects from pindolol. Of the 9 patients who stopped taking pindolol, 3 were switched to another regimen for recurrent symptoms, 2 stopped because of side effects, and 4 did not comply with the regimen. In conclusion, pindolol appears to be safe and effective as initial treatment for vasovagal syncope.