OBJECTIVE The objective of this retrospective study is to compare the medical treatment of neonatal narcotic abstinence syndrome with clonidine and chloral hydrate with the commonly used combination therapy of morphine and phenobarbital. METHODS From 1998 to 2008, a total of 133 newborns suffering from neonatal narcotic abstinence syndrome were treated at our clinic. All of these patients were born to mothers who had received methadone substitution for drug addiction during the course of pregnancy. RESULTS Twenty-nine patients received clonidine and chloral hydrate, and 64 patients were treated with morphine and phenobarbital for abstinence syndrome. The duration of treatment was significantly shorter in the clonidine/chloral hydrate group (median: 14 days vs. 35 days). Correspondingly, the period of hospitalization was also considerably shorter in the clonidine/chloral hydrate group (median: 32 days vs. 44 days). In addition, patients in the clonidine/chloral hydrate group exhibited markedly reduced withdrawal symptoms. CONCLUSIONS This study suggests that a treatment of neonatal abstinence syndrome with clonidine in omission of opiates is possible without causing short-term adverse cardiovascular effects. Considering the retrospective design of the study, controlled and prospective trials are needed.