About 20% of adults faint recurrently. These patients are often highly symptomatic, have problems with employment and driving, can be injured, and have poor quality of life. There are few therapies that have withstood the test of randomized clinical trials. the investigators will conduct a prospective, randomized, parallel, double-blind, proof-of-concept study that tests the hypothesis that serotonin 5HT3 receptor inhibition with ondansetron prevents tilt-induced vasovagal syncope (VVS) and pre-syncope in patients with clinical VVS. A total of 70 patients with quantitative clinical diagnostic criteria for VVS and at least 1 syncopal spell in the preceding year will be randomized in a double-blind acute phase 2 study to ondansetron 8 mg PO BID x 2 doses or matching placebo. The endpoint will be presyncope or syncope associated with diagnostic hemodynamic changes. These data should provide useful preliminary data as a foundation on which to conduct a subsequent randomized clinical trial.