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The aim of this study was to evaluate the effect of the Quebec Healthy Enterprise Standard (QHES) on adverse physical and psychosocial work factors and work-related musculoskeletal problems (WMSP).Workers of 10 organizations completed questionnaires before (n = 2849) and 2 to 3 years following (n = 2560) QHES implementation. Outcomes were assessed using validated instruments.Workers exposed to adverse physical and psychosocial work factors had a higher prevalence of WMSP. After interventions, the prevalences of one adverse physical and three adverse psychosocial work factors were lower among workers exposed to interventions. Among men exposed to physical and psychosocial interventions, the lower prevalence of neck WMSP is compatible with a beneficial intervention effect. Other results generally showed few effects on WMSP.Results suggest that QHES implementation lead to a decrease in some adverse physical and psychosocial work factors. Few effects were observed on WMSP.