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The prevention of deforestation and promotion of afforestation have often been cited as strategies to slow global warming. Deforestation releases CO2 to the atmosphere, which exerts a warming influence on Earth’s climate. However, biophysical effects of deforestation, which include changes in land surface albedo, evapotranspiration, and cloud cover also affect climate. Here we present results from several large-scale deforestation experiments performed with a three-dimensional coupled global carbon-cycle and climate model. These simulations were performed by using a fully three-dimensional model representing physical and biogeochemical interactions among land, atmosphere, and ocean. We find that global-scale deforestation has a net cooling influence on Earth’s climate, because the warming carbon-cycle effects of deforestation are overwhelmed by the net cooling associated with changes in albedo and evapotranspiration. Latitude-specific deforestation experiments indicate that afforestation projects in the tropics would be clearly beneficial in mitigating global-scale warming, but would be counterproductive if implemented at high latitudes and would offer only marginal benefits in temperate regions. Although these results question the efficacy of mid- and high-latitude afforestation projects for climate mitigation, forests remain environmentally valuable resources for many reasons unrelated to climate.