Following clonidine ingestion, naloxone is seldom administered as it is considered ineffective in reversing somnolence, bradycardia, or hypotension. However, this conclusion has been based on administration of small doses (2 mg or less) of naloxone. The somnolence is frequently treated with endotracheal intubation (ETI), a procedure with significant morbidity. We aimed to determine if naloxone administration reversed the effects of clonidine or caused any adverse effects. We performed a retrospective descriptive cohort (IRB approved) of hospital medical records for pediatric patients (6 months-16 years) with clonidine exposure. Demographics, history, co-ingestants, clinical data, treatments, and outcome were recorded in a de-identified database. The most common clinical findings in the 52 patients were sedation (n = 51), bradycardia (n = 44), and hypotension (n = 11). Of 51 somnolent patients, naloxone administration awoke 40 patients, five of which had co-ingestants. Nine patients experienced recurrent sedation that resolved with a repeat bolus of naloxone. Twenty somnolent bradycardic patients (11 less than 3 years old) received 10 mg naloxone via intravenous bolus. Thirteen awoke; bradycardia persisted in six of the awake patients. Of the remaining 31 patients, 22 awoke following 6 mg or less of naloxone. Naloxone reversed hypotension in 7 of 11 hypotensive patients. Only one hypotensive patient (with a coingestion) received vasopressors for hypotension. Three awake normotensive patients received vasopressors for bradycardia. Seven patients awoke and had normal vital signs following naloxone administration, but were chemically sedated and intubated for transport. There were no adverse events following the administration of any dose of naloxone. Administration of naloxone to somnolent pediatric patients with clonidine toxicity awoke the majority (40/51) and resolved bradycardia and hypotension in some. Persistent bradycardia was benign. Hypotension was rare and clinically insignificant. No adverse effects occurred in any patient including the 21 patients who received 10 mg naloxone. Morbidity in this overdose may be due to ETI, a procedure that could be prevented if high-dose naloxone (10 mg) were administered. Administration of high-dose naloxone should be considered in all children with clonidine toxicity.