Objective: Methadone has been associated with prolongation of the QTc interval (QTc) on electrocardiogram (ECG). In infants, the effects of methadone on the QTc are not well described. Our study's objective is to evaluate the QTc in infants being treated with methadone. Methods: We conducted a retrospective study in infants receiving methadone. We collected demographic data, methadone dose, and QTc. A blinded-to-disease-state pediatric electrophysiologist determined the QTc. Baseline ECG was defined as an ECG obtained while not on methadone therapy, and QTc on baseline ECG was compared with treatment QTc. A significant change was defined as any absolute QTc greater than 500 or a QTc greater than 460 with an increase from baseline of greater than 40 ms. Results: A total of 44 infants comprised the study population. The mean gestational age was 32.3 ± 5.51 weeks. The median age of initiation was 66 days. The median dose was 0.52 mg/kg/day in oral methadone equivalents. Nine patients were on high dose methadone (>1 mg/kg/day in oral methadone equivalents). The mean baseline QTc was 421 ± 27 and the mean change on methadone was −2 ms. No patient had a QTc greater than 500 on methadone. One patient had a QTc of 467 and 46 ms change from baseline, with no clinically significant impact. Conclusion: In our study population, methadone did not significantly prolong the QTc. Further prospective study is warranted to determine the utility and frequency of ECGs in infants receiving methadone.