BACKGROUND: Several studies have illustrated the efficacy of pregabalin in decreasing postoperative opioid use in adults undergoing orthognathic surgery. We aimed to study the effects of a single dose of preoperative pregabalin on total opioid consumption after orthognathic surgery in individuals with cleft lip and palate. METHODS: This is a retrospective cohort study of consecutive patients who underwent Le Fort I midface advancement between June 2012 and July 2019. All patients had a diagnosis of cleft lip and palate. The treatment group received a 1-time preoperative dose of pregabalin; the control group did not. Total morphine milligram equivalent (MME) consumption was calculated by adding intraoperative and postoperative opioid use during admission. RESULTS: Twenty-three patients were included in this study; 12 patients received pregabalin. The pregabalin group had significantly lower total opioid consumption (total MME 70.95 MME; interquartile range [IQR]: 24.65-150.17) compared to the control group (138.00 MME; IQR: 105.00-232.48) (MU = 31.00, P = 0.031). The difference in mean pain scores in the treatment group (3.21 ± 2.03) and the control group (3.71 ± 2.95) was not statistically significant (P = 0.651, 95% confidence interval -1.75 to 2.75). CONCLUSIONS: A 1-time preoperative dose of pregabalin before orthognathic surgery in patients with cleft lip and palate reduced total opioid consumption during admission without increasing patient pain. A single preemptive dose of pregabalin should be considered an effective adjunct to pain management protocols in patients undergoing orthognathic surgery.