ObjectiveEnhanced recovery after surgery (ERAS) guidelines have been successfully applied to children and neonates. There is a need to provide evidence-based consensus recommendations to manage neonatal pain perioperatively to ensure adequate analgesia while minimising harmful side effects.MethodsFollowing a stakeholder needs assessment, an international guideline development committee (GDC) was established. A modified Delphi consensus iteratively defined the scope of patient and procedure inclusion, topic selection and recommendation content regarding the pharmacologic management of neonatal pain. Critical appraisal tools assessed the relevance and quality of full-text studies. Each recommendation underwent a formal Grades of Recommendation, Assessment, Development and Evaluation (GRADE) assessment of the quality of evidence and expert consensus was used to determine the strength of recommendations.ResultsThe GDC included paediatric anaesthesiologists, surgeons, and ERAS methodology experts. The population was defined as neonates at >32 weeks gestational age within 30 days of life undergoing surgery or painful procedures associated with surgery. Topic selection targeted pharmacologic opioid-minimising strategies. A total of 4249 abstracts were screened for non-opioid analgesia and 738 abstracts for the use of locoregional analgesia. Full-text review of 18 and 9 articles, respectively, resulted in two final recommendations with a moderate quality of evidence to use regular acetaminophen and to consider the use of locoregional analgesia. There was inadequate evidence to guide the use of other non-opioid adjuncts in this population.ConclusionsEvidence-based, ERAS-driven consensus recommendations were developed to minimise opioid usage in neonates. Further research is required in this population to optimize multimodal strategies for pain control.