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Repetitive and monotonous work, especially manual work, is very common in modern industrial operations, resulting in an increased risk of musculoskeletal disorders. It is therefore important to find an appropriate intervention counteracting or preventing the repetitive and monotonous character of work tasks, for example by work-breaks. This review aims to assess the effectiveness of work-breaks (compared to no work-breaks or regular work-break schedules) for preventing work-related musculoskeletal disorders in workers. A work-break can be defined as any scheduled work-interruption that is not related to work, which includes the following characteristics: frequency (amount, timing), duration, or type (e.g. active or passive).We will search the literature (e.g., CENTRAL, PubMed) for randomised, quasi-randomised, and cluster-randomised studies without language restrictions. We will include trials that have enrolled adult workers without musculoskeletal symptoms and that have assessed one or more of the following work-break interventions: changes in break duration, frequency, timing, or type. Two review authors will independently consider retrieved records for eligibility and extract the data.The extracted data will be summarised and two review authors will independently assess the risk of bias for each study regarding random sequence allocation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective outcome reporting (criteria as outlined in the Cochrane Handbook). The meta-analysis will initially be performed including all studies. Thereafter a sensitivity analysis confined to trials at low risk of bias will be conducted. The heterogeneity of the results of included studies will be assessed by visual inspection of the forest plots and consideration of trial characteristics, e.g. work-break characteristics.The results of this Cochrane Review will provide insights into the effectiveness of work-break interventions and provide direction for optimising current prevention approaches and help prioritise future fields of research.