To determine the safety, efficacy, and outcomes of bradycardia, hypotension, and hypertension with dexmedetomidine (DEX), a recently approved sedative used for procedural sedation that has not been described previously for pediatric nuclear medicine imaging. Between March 2005 and August 2011, 669 patients (mean age, 5.7 years ± 4.5 [standard deviation]; median age, 4.5 years; age range, 0.1-22.5 years) received DEX in this HIPAA-compliant study. Sedation was administered with DEX, an α-2 adrenergic agonist, as an intravenous bolus (2 μg per kilogram of body weight) over a 10-minute period; this was followed by continuous infusion at a rate of 1 μg/kg/h until imaging was complete. The bolus could be repeated up to two times, if needed, to achieve the targeted level of a Ramsay sedation score of 4. After institutional review board approval, collected quality assurance data were reviewed. Adequate sedation was achieved within 8.6 minutes ± 4.6 (median, 8.0 minutes; range, 1.0-40.0 minutes) on average in studies that averaged 41.3 minutes ± 25.5 (median, 31.5 minutes; range, 9.0-183.0 minutes). Of 669 studies, 667 (99.7%) were completed successfully. Six children (0.9%) had brief periods of oxygen desaturation below 95%, none of which required airway intervention. Hypotension, hypertension, and bradycardia (all defined as deviations of more than 20% from age-adjusted awake norms), occurred in 58.7% (n = 393), 2.1% (n = 14), and 4.3% (n = 29) of patients, respectively. Both hypotension and bradycardia were related to age (P = .033 and P = .002, respectively); older children tended to experience more of these events. None of these fluctuations required pharmacologic therapy. Discharge criteria (modified Aldrete score ≥ 9) were met, on average, within 41.4 minutes ± 27.9 (median, 36.0 minutes; range, 1.0-220.0 minutes). DEX offers advantages for pediatric sedation for nuclear medicine imaging. DEX produces a condition similar to natural sleep, with no detrimental effect on respiration. The hemodynamic variability anticipated with DEX did not require pharmacologic treatment, and the drug was well tolerated.