There is disagreement about allowing propofol sedation for research magnetic resonance imaging/spectroscopy (MRI/MRS) in children. Our study is the first to provide relevant safety and efficacy data. With institutional approval, 108 research MRI/MRS procedures under propofol sedation were performed longitudinally on children at ages 3-4 years (N=59) and 6-7 years (N=49). Sedation parameters, physiological values, and outcome data were collected. Success rate for acquisition of satisfactory quality MRI/MRS during propofol sedation was compared with that in typically developing, age-matched sleeping children. Only 5 minor events (2 with need to insert an oral airway, 2 with premature termination of study, 1 with bradycardia not requiring treatment) and no major events occurred. These safety/efficacy data are equal to or better than previously reported with propofol for clinically indicated procedures. A high percentage of parents of children participating in MRI/MRS studies at 3-4 years of age returned with their child at 6-7 years of age, and longitudinal follow-up was not adversely impacted by their child's experience with sedation. The success rate of data acquisition was significantly higher during propofol sedation (98%) than during late-night sleep studies in typically developing children (30%-50%). We conclude that propofol sedation for research MRI/MRS is safe and effective when children of appropriate ASA class are selected, supplemental oxygen is delivered, and sedation and monitoring are done by an experienced anesthesiologist.