AIMS AND OBJECTIVES:To extract, examine and report the highest available levels of evidence from healthcare disciplines in the use of simulation-based education as substitution for clinical placement in prelicensure programmes. BACKGROUND:Simulation is widely employed across prelicensure health professional education to create safe, realistic clinical learning experiences for students. Whether simulation can be employed to substitute for actual clinical placement, and if so, in what proportion, replacement ratio and duration, is unclear. METHODS:A systematic review and quality appraisal of primary studies related to prelicensure students in all health disciplines, guided by the PRISMA checklist. RESULTS:Ten primary studies were included, representing 2,370 students from three health disciplines in four countries. Nine studies were experimental and quasi-experimental and methodological quality was assessed as moderate to high with good to very good inter-rater agreement. Direct substitution of simulation for clinical practice ranged from 5% to 50%. With one exception, replacement ratios were 1:1 and duration of replacement ranged from 21 hr-2 years. Levels of evaluation included measures of reaction, knowledge and behaviour transfer; no negative outcomes were reported. We appraised practicalities for design of substitution, design limitations and knowledge transfer to accreditation standards for prelicensure programmes. CONCLUSIONS:This review synthesised highest levels and quality of available evidence for substitution of simulation for clinical placement in health professional education. Included studies were heterogenous in simulation interventions (proportion, ratio and duration) and in the evaluation of outcomes. Future studies should incorporate standardised simulation curricula, widen the health professions represented and strengthen experimental designs. RELEVANCE TO CLINICAL PRACTICE:Current evidence for clinical educational preparation does not appear to be translated into programme accreditation standards governing clinical practice experience for prelicensure programmes in relevant jurisdictions. Overall, a stronger evidence base is necessary to inform future curricula and policy development, to strengthen clinical practice in health.