BACKGROUND Inappropriate antibiotic use can cause harm and promote antimicrobial resistance, which has been declared a major health challenge by the World Health Organization. In Australian residential aged care facilities (RACFs), the most common indications for antibiotic prescribing are for infections of the urinary tract, respiratory tract and skin and soft tissue. Studies indicate that a high proportion of these prescriptions are non-compliant with best prescribing guidelines. To date, a variety of interventions have been reported to address inappropriate prescribing and overuse of antibiotics but with mixed outcomes. This study aims to identify the impact of a set of sustainable, multimodal interventions in residential aged care targeting three common infection types. METHODS This protocol details a 20-month stepped-wedge cluster-randomised trial conducted across 18 RACFs (as 18 clusters). A multimodal multi-disciplinary set of interventions, the 'AMS ENGAGEMENT bundle', will be tailored to meet the identified needs of participating RACFs. The key elements of the intervention bundle include education for nurses and general practitioners, telehealth support and formation of an antimicrobial stewardship team in each facility. Prior to the randomised sequential introduction of the intervention, each site will act as its own control in relation to usual care processes for antibiotic use and stewardship. The primary outcome for this study will be antibiotic consumption measured using defined daily doses (DDDs). Cluster-level rates will be calculated using total occupied bed numbers within each RACF during the observation period as the denominator. Results will be expressed as rates per 1000 occupied bed days. An economic analysis will be conducted to compare the costs associated with the intervention to that of usual care. A comprehensive process evaluation will be conducted using the REAIM Framework, to enable learnings from the trial to inform sustainable improvements in this field. CONCLUSIONS A structured AMS model of care, incorporating targeted interventions to optimise antimicrobial use in the RACF setting, is urgently needed and will be delivered by our trial. The trial will aim to empower clinicians, residents and families by providing a robust AMS programme to improve antibiotic-related health outcomes. BACKGROUND US National Library of Medicine Clinical Trials.gov ( NCT04705259 ). Prospectively registered in 12th of January 2021.