BACKGROUND: Opioids and benzodiazepines have been the mainstay of neonatal analgesia and sedation. However, based on evidence in neonatal animals, these drugs may be deleterious for the developing brain. Dexmedetomidine (DEX), a central alpha-2 agonist, has sedative and analgesic effects and has been shown to be neuroprotective in animal models. Despite increasing use of DEX in newborns, there is a paucity of data regarding its safety and efficacy in this population. OBJECTIVES: The impact of using DEX in postsurgical neonates, either alone or with opioid infusions, for sedation/analgesia was evaluated. The cumulative dose of opioids among patients who did or did not receive DEX was calculated to examine the hypothesis that the addition of DEX can reduce the patient exposure to opioids without significantly increasing side effects and providing adequate sedation and pain control. METHODOLOGY: This was a retrospective cohort study in which patients were matched by postnatal age and surgical procedure into 2 groups. One group received DEX in the regimen for treatment of pain or sedation after a surgical procedure, and the other group received no DEX. Episodes of bradycardia, respiratory depression and hypotension, and the cumulative dose of opioids and number of supplemental doses administered in both groups were documented. RESULTS: Although there was no difference in gestational age or weight at birth between the DEX and no-DEX groups, the DEX group's median postconceptional date was older at the time of surgery (39.6 vs 37.4 weeks; p = 0.003). Patients in the DEX group experienced more episodes of bradycardia (12.8% vs 5.1%; p = 0.01). There was no difference between groups in episodes of hypotension or respiratory depression. The cumulative dose of opioids was significantly lower in the DEX group compared with the no-DEX group (1155 mcg/kg vs 1841 mcg/kg; p = 0.01). There was no difference in the number of supplemental doses of opioids given between the groups. CONCLUSIONS: The addition of DEX to opioid infusions resulted in a significant decrease in the cumulative dose of opioids but was associated with more episodes of bradycardia than opioids alone.