Most studies report the efficacy of only a single drug to achieve sedation in a broad age range of children. In clinical practice, a variety of sedative and anesthetic regimes are monitored by nurses and physicians. In this study we report the efficacy of a tiered approach to monitoring and sedation in infants. Two-hundred-fifty-eight infants who required magnetic resonance imaging (MRI) studies received either oral chloral hydrate (n = 102) or bolus doses of IV pentobarbital (n = 67) monitored by nurses or IV propofol infusion (n = 68) titrated by physicians. Fewer cardiorespiratory events were observed in the chloral hydrate group (2.9%) compared to pentobarbital (13.4%) and propofol groups (13.6%); P < 0.05, propofol versus chloral hydrate. Infants who received propofol were ready to begin MRI scanning earlier (mean 9.1 +/- 6.7 min) than infants who received oral chloral hydrate (mean 23.5 +/- 13.4 min; P < 0.05). The time to discharge was longest in the pentobarbital (mean 80.3 +/- 39.2 min) and shortest in the propofol group (mean 53.9 +/- 30.1 min; P < 0.05). Infants in the chloral hydrate group moved more frequently (22.5%) during MRI scanning (with four sedation failures of 102) compared to 12.2% in the pentobarbital group and 1.4% in the propofol group (P < 0.001).