Variability in the pharmacokinetics and pharmacodynamics of oxycodone in pediatric surgery could be due to genetic polymorphisms. The association between clinical outcomes and pharmacogenes in 89 children undergoing major surgery was studied. Polymorphisms in OPRM1, PXR, COMT and ABCB1 were shown to be associated with average morphine equivalent dose, length of hospital stay and maximum surgical pain. This study demonstrated novel associations between the above pharmacogenes, oxycodone’s pharmacokinetics, and postoperative outcomes in children.