Critically ill children are treated with opioid medication in an attempt to decrease stress and alleviate pain during prolonged pediatric intensive care. This treatment plan places children at risk for opioid dependency. Once dependent, children need to be weaned or risk development of a withdrawal syndrome on abrupt cessation of medication. We enrolled opioid-dependent children into a prospective, randomized trial of 5- versus 10-day opioid weaning using oral methadone. Children exposed to opioids for an average of 3 wk showed no difference in the number of agitation events requiring opioid rescue (3 consecutive neonatal abstinence scores >8 every 2 h) in either wean group. Most of the events requiring rescue occurred on day 5 and 6 of the wean in both treatment groups. Patients may be able to be weaned successfully in 5 days once converted to oral methadone, with a follow-up period after medication wean to observe for a delayed withdrawal syndrome.