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The aim of this systematic review was to evaluate the cost-effectiveness of occupational safety and health interventions from the employer perspective.A comprehensive literature search (2005 to 2016) in five electronic databases was conducted. Pre-2005 studies were identified from the reference lists of previous studies and systematic reviews, which have similar objective to those of this search.A total of 19 randomized controlled trials and quasi-experimental studies were included, targeting diverse health problems in a number of settings. Few studies included organizational-level interventions. When viewed in relation to the methodological quality and the sufficiency of economic evidence, five of 11 cost-effective occupational safety and health (OSH) interventions appear to be promising.The present systematic review highlights the need for high-quality economic evidence to evaluate the cost-effectiveness of OSH interventions, especially at organizational-level, in all areas of worker health.