Methadone is commonly prescribed for prevention of iatrogenic opioid abstinence syndrome (IOAS) in critically ill children. However, there is a paucity of data on the recommended initial dosage requirements. Data was retrospectively collected from January--December 31, 2008 and included demographics, methadone regimen, and IOAS symptoms. The primary objective was to determine the initial methadone dosing utilized (i.e., mg/kg/day) and the impact that this had on the number of dosage changes required for prevention of IOAS in patients < 18 yr within 72 hr following discontinuation of opioid continuous infusion (CI). Secondary objectives included a comparison of methadone dose changes within 72 hr of intravenously opioid discontinuation and opioid CI requirements based on initial doses above and below the median level (i.e., mg/kg/day). Between-group analysis was performed using descriptive and inferential statistics. A step-wise regression was employed to assess relationships between the initial dose (mg/kg/day) and several independent variables. Fifty-five patients were included for analysis. The median initial dose was 0.84 mg/kg/day. The “low-dose” group included patients receiving < 0.84 mg/kg/day (n = 27); the “high-dose” group included patients receiving &≥; 0.84 mg/kg/day (n = 28). The majority of patients (81.8%) received doses every 6 hr. Twenty-three patients (41.8%) developed IOAS and required an increase in dose while six patients (10.9%) required a decrease. No significant differences were found between groups. The cumulative and peak fentanyl CI doses were the only significant predictors of total mg/kg/day dose of methadone (P < 0.01). The initial methadone dosage regimens varied greatly in our patients. Approximately half required a change in their methadone dose. Based on our findings and a review of the literature, there is not a one-size fits all approach for determination of the initial methadone dose. Adoption of a consistent monitoring tool should be utilized for all children across the continuum of care to prevent IOAS and the over-sedation noted with excessive methadone dosing.