Background: Inadequately controlled sternotomy pain after cardiac surgery can lead to delayed recovery and patient suffering. Preoperative intravenous methadone is effective for reducing both postoperative pain and opioid consumption. Despite ease of administration, the effects of preoperative oral methadone are not well described in the literature. Aims: This pilot study investigated the effect of preoperative oral methadone on pain scores, analgesia requirements, and opioid-induced side effects. Methods: A randomized double-blind placebo-controlled model was used with sampling of patients undergoing sternotomy for isolated coronary artery bypass graft (CABG) surgery (ClinicalTrials.gov registration no. NCT02774499). Participants were randomized to receive oral methadone (0.3 mg/kg) or oral placebo prior to entering the operating room. The primary outcome was pain scores on a 0-10 Verbal Rating Scale. Secondary outcomes included morphine requirements using patient-controlled analgesia (PCA), time to extubation, level of sedation, and side effects such as nausea, vomiting, pruritus, hypoventilation, and hypoxia over a 72-h monitoring time. Results: Twenty-one patients completed the study. Oral methadone did not reduce pain scores in the methadone group (P = 0.08). However, postoperative morphine requirement during the first 24 h was reduced by a mean of 23 mg in the methadone group (mean difference, -23; 99% confidence interval [CI], 37-13 mg; P < 0.005). No reduction in pain scores or PCA morphine was observed beyond 24 h postoperatively. There was no difference in incidence of opioid-related side effects between groups throughout the postoperative period. Conclusions: Though preoperative oral methadone did not reduce pain scores, morphine requirements were reduced in the first 24 h post-CABG.