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This study, carried out within the FP7-ENV-2010 CLUVA project, aimed to classify and map sensitivity to desertification in peri-urban areas of Ouagadougou (Burkina Faso) and Saint Louis (Senegal) African cities by applying a multifactor approach based on the EU MEDALUS key indicators. All local data allowed identifying Environmentally Sensitive Areas (ESAs) and an Index of Environmentally Sensitive Areas (ESAI). The studied peri-urban areas had an overall high sensitivity to desertification. In Ouagadougou, the most sensitive areas were those poorly vegetated and overexploited by an ever-increasing demographic pressure; in Saint Louis, the critical zones were mostly located in the northern part of the studied area, strongly characterized by both shallow sandy soils and vegetation overexploitation by grazing and domestic. This study suggests that ESAs maps can represent a valuable tool to promote and orientate effective policies of desertification prevention and mitigation for sustainable development of the African rural-urban interfaces.