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BackgroundDespite the well-known beneficial health effects of physical activity (PA), the majority of Dutch primary school children do not meet the recommended PA guidelines. Although there is growing evidence on the effectiveness of exergames for PA in children, there is limited evidence on their effect on health outcomes, such as cardiovascular health and health-related quality of life (HRQOL), and on factors influencing their effectiveness and feasibility. The exergame BOOSTH uses a wrist-worn activity tracker to measure steps per day. As a reward for the performed PA, children can unlock levels in the online BOOSTH game. In addition, “BOOSTH battle” enables competition between groups. ObjectiveThis protocol describes a cluster randomized controlled trial in 16 primary schools in the Netherlands investigating the effect of BOOSTH on moderate-to-vigorous PA (MVPA) using accelerometry. Secondary aims are to investigate the feasibility of BOOSTH (mixed methods: questionnaires and focus group interviews) and its effect on cardiovascular risk factors (anthropometrics, blood pressure, and retinal microvasculature) and HRQOL. MethodsStratification variables and relevant variables related to outcomes (such as BMI [z-score], sex, age, and parenting style) and/or missingness will be taken into account. Measurements will be performed at baseline and after 3, 6, and 12 months. ResultsThe study has received funding from Province Limburg (SAS-2015-04956) and received ethical approval from the Medical Ethics Committee of Maastricht University Medical Centre (METC172043/NL64324.068.17). The results of the analyses are expected to be published in 2021. ConclusionsWith this study, the ability of the exergame BOOSTH to increase PA and improve health in children of primary school age will be investigated. The insights into effectiveness and feasibility will result in scientific and societal recommendations, which could potentially contribute to widespread implementation of exergames for children. Trial RegistrationClinicalTrials.gov NCT03440580; https://clinicaltrials.gov/ct2/show/NCT03440580. International Registered Report Identifier (IRRID)DERR1-10.2196/24035