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Physical activity and diet are major modifiable risk factors for chronic disease and have been shown to be associated with neighborhood built environment. Systematic review evidence from longitudinal studies on the impact of changing the built environment on physical activity and diet is currently lacking. A systematic review of natural experiments of neighborhood built environment was conducted. The aims of this systematic review were to summarize study characteristics, study quality, and impact of changes in neighborhood built environment on physical activity and diet outcomes among residents. Natural experiments of neighborhood built environment change, exploring longitudinal impacts on physical activity and/or diet in residents, were included. From five electronic databases, 2084 references were identified. A narrative synthesis was conducted, considering results in relation to study quality. Nineteen papers, reporting on 15 different exposures met inclusion criteria. Four studies included a comparison group and 11 were pre-post/longitudinal studies without a comparison group. Studies reported on the impact of redeveloping or introducing cycle and/or walking trails (n = 5), rail stops/lines (n = 4), supermarkets and farmers’ markets (n = 4) and park and green space (n = 2). Eight/15 studies reported at least one beneficial change in physical activity, diet or another associated health outcome. Due to limitations in study design and reporting, as well as the wide array of outcome measures reported, drawing conclusions to inform policy was challenging. Future research should consider a consistent approach to measure the same outcomes (e.g., using measurement methods that collect comparable physical activity and diet outcome data), to allow for pooled analyses. Additionally, including comparison groups wherever possible and ensuring high quality reporting is essential. View Full-Text