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To summarise the literature on the economic burden of physical inactivity in populations, with emphases on appraising the methodologies and providing recommendations for future studies.Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number CRD42016047705).Electronic databases for peer-reviewed and grey literature were systematically searched, followed by reference searching and consultation with experts.Studies that examined the economic consequences of physical inactivity in a population/population-based sample, with clearly stated methodologies and at least an abstract/summary written in English.Of the 40 eligible studies, 27 focused on direct healthcare costs only, 13 also estimated indirect costs and one study additionally estimated household costs. For direct costs, 23 studies used a population attributable fraction (PAF) approach with estimated healthcare costs attributable to physical inactivity ranging from 0.3% to 4.6% of national healthcare expenditure; 17 studies used an econometric approach, which tended to yield higher estimates than those using a PAF approach. For indirect costs, 10 studies used a human capital approach, two used a friction cost approach and one used a value of a statistical life approach. Overall, estimates varied substantially, even within the same country, depending on analytical approaches, time frame and other methodological considerations.Estimating the economic burden of physical inactivity is an area of increasing importance that requires further development. There is a marked lack of consistency in methodological approaches and transparency of reporting. Future studies could benefit from cross-disciplinary collaborations involving economists and physical activity experts, taking a societal perspective and following best practices in conducting and reporting analysis, including accounting for potential confounding, reverse causality and comorbidity, applying discounting and sensitivity analysis, and reporting assumptions, limitations and justifications for approaches taken. We have adapted the Consolidated Health Economic Evaluation Reporting Standards checklist as a guide for future estimates of the economic burden of physical inactivity and other risk factors.