The purpose of this prospective study was to determine the safety and efficacy of chloral hydrate sedation in children with known or suspected congenital heart disease. The study population included 405 children with a median age of 13 months (3 weeks to 14 years). Cyanotic heart disease was present in 64 of the children. The median dosage of chloral hydrate given was 77 mg/kg, with a range of 25 to 125 mg/kg. Sedation was achieved in 397 (98%) of the children. The complete study time averaged 2.2 hours (range, 1.6 to 5.2 hours). The time to achieve sedation was 30 minutes or less in 82%, more than 30 but less than 60 minutes in 12%, and more than 60 minutes in 4%; 2% failed to achieve sedation. Children aged 3 years or younger were more likely to be successfully sedated with chloral hydrate (p = 0.003). The type of heart disease did not affect the success of sedation. No child had a clinically significant change in heart rate or blood pressure during sedation; however, oxygen saturation decreased in 24 (6%) of 397 children successfully sedated. Decreases in oxygen saturation occurred more commonly in children with trisomy 21 (7/13) than in children without genetic syndromes (17/384). Vomiting occurred in 23 (6%) of the 405 study subjects, usually immediately after drug administration. Chloral hydrate is a safe and effective agent for sedation of children with known or suspected congenital heart disease who are undergoing echocardiography in the outpatient cardiology clinic.