Objective: To assess clinical response of dexmedetomidine alone or in combination with conventional sedatives/analgesics after cardiac surgery. Design: Retrospective study. Setting: Pediatric cardiac intensive care unit. Patients: Infants and neonates after cardiac surgery. Measurements and Main Results: We identified 80 patients including 14 neonates, at mean age and weight of 4.1 +/- 3.1 months and 5.5 +/- 2 kg, respectively, who received dexmedetomidine for 25 +/- 13 hours at an average dose of 0.66 +/- 0.26 mu g.kg(-1)-hr(-1). Overall normal sleep to moderate sedation was documented 94% of the time and no pain to mild pain for 90%. Systolic blood pressure (SBP) decreased from 89 +/- 15 mm Hg to 85 +/- 11 mm Hg (p = .05), heart rate (HR) from 149 +/- 22 bpm to 129 +/- 16 bpm (p < .001), and respiratory rate (RR) remained unchanged. When baseline arterial blood gases were compared with the most abnormal values, pH decreased from 7.4 +/- 0.07 to 7.37 +/- 0.05 (p = .006), PO2 from 91 +/- 67 mm Hg to 66 +/- 29 mm Hg (p = .005), and CO2 increased from 45 +/- 8 mm Hg to 50 +/- 12 mm Hg (p = .001). At the beginning of the study, 37 patients (46%) were mechanically ventilated; and at 48 hours, 13 patients (16%) were still intubated and five patients failed extubation. Three groups of patients were identified: A, dexmedetomidine only (n = 20); B, dexmedetomidine with sedatives/analgesics (n = 38); and C, dexmedetomidine with both sedatives/analgesics and fentanyl infusion (n = 22). The doses of dexmedetomidine and rescue sedatives/analgesics were not significantly different among the three groups but duration of dexmedetomidine was longer in group C vs. A (p = .03) and C vs. B (p = .002). Pain, sedation, SBP, RR, and arterial blood gases were similar. HR was higher in group C vs. B (p = .01). Comparison between neonates and infants showed that infants required higher dexmedetomidine doses, 0.69 +/- 25 mu g.kg(-1)-hr(-1), and vs. 0.47 +/- 21 mu g.kg(-1).hr(-1) (p = .003) and had lower FIR (p = .01), and RR (p = .009), and higher SBP (p < .001). Conclusions: Dexmedetomidine use in infants and neonates after cardiac surgery was well tolerated in both intubated and nonintubated patients. It provides an adequate level of sedation/analgesia either alone or in combination with low-dose conventional agents. (Pediatr Crit Care Med 2009; 10:654-660)