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Road construction and paving bring socio-economic benefits to receiving regions but can also be drivers of deforestation and land cover change. Road infrastructure often increases migration and illegal economic activities, which in turn affect local hydrology, wildlife, vegetation structure and dynamics, and biodiversity. To evaluate the full breadth of impacts from a coupled natural-human systems perspective, information is needed over a sufficient timespan to include pre- and post-road paving conditions. In addition, the spatial scale should be appropriate to link local human activities and biophysical system components, while also allowing for upscaling to the regional scale. A database was developed for the tri-national frontier in the Southwestern Amazon, where the Inter-Oceanic Highway was constructed through an area of high biological value and cultural diversity. Extensive socio-economic surveys and botanical field work are combined with remote sensing and reanalysis data to provide a rich and unique database, suitable for coupled natural-human systems research.