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Sunil Shrestha,1 Asmita Priyadarshini Khatiwada,2 Binaya Sapkota,3 Simit Sapkota,4,5 Prabhat Poudel,6 Bhuvan KC,7,8 Siew Li Teoh,1 Ali Qais Blebil,1 Vibhu Paudyal9 1School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, 47500, Malaysia; 2Department of Health Outcomes Research and Policy, Harrison College of Pharmacy, Auburn University, Auburn, AL, USA; 3Department of Pharmaceutical Sciences, Nobel College, Kathmandu, Nepal; 4Department of Clinical Oncology, Civil Service Hospital, Minbhawan, Kathmandu, Bagmati Province, Nepal; 5Department of Clinical Oncology, Kathmandu Cancer Center, Tathali, Bagmati Province, Nepal; 6Nepal Medical College Hospital, Kathmandu, Province Bagmati, Nepal; 7College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, QLD, Australia; 8Faculty of Pharmacy and Pharmaceutical Sciences Monash University Parkville Campus Parkville, Melbourne, VIC 3052, Australia; 9School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKCorrespondence: Sunil Shrestha; Vibhu Paudyal, Tel +60 102874113, Email Sunil.shrestha@monash.edu; sunilcresta@gmail.com; v.paudyal@bham.ac.ukIntroduction: Opioid stewardship has been widely used to promote rational use, monitoring and discontinuation of opioid therapy; however, its definition and scope of practice remain unclear.Objective: To synthesize definitions of opioid stewardship proposed by clinical practice guidelines and professional societies, and to offer a proposal for a universally acceptable definition.Methods: Systematic literature searches were performed (earliest records to May 2022) in six databases (MEDLINE, EMBASE, APA PsycINFO, Scopus, and CENTRAL) and grey sources guidelines development bodies and professional societies through Google. The conventional but widely applied content analysis and word frequencies were used to analyze the definitions and scope of practice.Results: After removing duplicates, 449 articles were retrieved (439 databases and registers and 11 from other sources), 19 of which included a definition of “opioids stewardship”. A total of 12 themes was identified in the definitions, including 1) improvement or appropriateness of prescribing opioids use, 2) mitigation of risk from opioids, 3) monitoring opioid use, 4) evaluation of opioid use, 5) judicious opioid use, 6) appropriateness of opioid disposal, 7) identification and treatment of opioid use disorder, 8) reduction in mortality associated with opioid overdoses, 9) appropriate procurement practices, 10) appropriate storage, 11) promoting better communications between patients and prescribers including education provision and 12) patient-centered decision-making.Conclusion: Opioid stewardship is inconsistently defined across professional and research literature. While there is a greater focus on appropriateness and need for improvement of prescribing and monitoring of opioid use, the importance of communications between patients and prescribers, and patient involvement in both prescribing and deprescribing decision-making remains sparse. A comprehensive definition has been proposed as part of the work. There is a need to develop and validate the proposed definition and scope of practice to promote rationale for opioid prescribing, use and attainment of favourable outcomes through international consensus involving practitioners, researchers, and patients.Keywords: opioid, opioid stewardship, opioid stewardship definition, stewardship