Variability in the pharmacokinetics and pharmacodynamics of oxycodone in children undergoing surgery could be due to genetic polymorphisms. The authors studied the association between clinical outcomes and pharmacogenes in children undergoing major surgery. A total of 89 children (35 undergoing pectus excavatum repair and 54 undergoing spinal fusion) were recruited. SNP rs6902403 showed an association with maximum pain score and total morphine equivalent dose (p < 0.05). Other polymorphisms in SNP, , and were also shown to be associated with average morphine equivalent dose, length of hospital stay and maximum surgical pain (p < 0.05). This study demonstrates novel associations between the above pharmacogenes and oxycodone’s pharmacokinetics as well as postoperative outcomes in children. : NCT03495388 (ClinicalTrials.gov).