Background: Clinical aggression episodes, that is aggression and externalising behaviours that create risk, in acute care hospitals are increasing. Acute care staff are often not confident or trained in the management of aggression. Various aggression management training formats have been described in practice including face to face training, written learning resources, web- and media-based training resources, and simulation training. The aim of this systematic review is to assess whether simulation-based training is effective in increasing de-escalation knowledge, skills, and behaviour of staff working in the acute care setting., Methods: We designed and registered a study protocol for a systematic review of studies evaluating simulation-based training for the management of patients with aggression. We will include randomised controlled trials, non-randomised controlled trials, quasi-experimental studies, and observational studies including health care professionals and trainees in acute health care settings. Comprehensive searches will be conducted in the following databases (from January 1980 onwards): PubMed, MEDLINE, PsycINFO, CINAHL, and the Cochrane Library. The reference lists of selected studies, trial registers, and leading journals will also be searched. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential discrepancies will be resolved through discussion. The primary outcomes will include patient outcomes (e.g. frequency of clinical aggression), quality of care (e.g. frequency of emergency situations, physical/chemical/mechanical restraint), and adverse effects (e.g. patient/family complaints, patient harms, staff harms). Secondary outcomes will include workplace resource use, health care provider-related outcomes, knowledge (de-escalation techniques), performance, attitudes, and satisfaction. The study methodological risk of bias will be appraised using appropriate tools. A narrative synthesis will be performed for included studies. If feasible, we will conduct random-effects meta-analysis of data. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. participant characteristics, interventions, and follow-up)., Discussion: This systematic review will identify, evaluate, and integrate the evidence on simulation-based training programmes for acute care health professionals on managing clinical aggression. The results of this study will inform the implementation of effective training strategies. Implications for future research will be discussed., Systematic Review Registration: PROSPERO registration number CRD42020151002.