The Brazilian Cerrado is one of the most endangered biomes in the world. We evaluated the sustainability of leaf harvest in one of the most important Cerrado tree species, Stryphnodendron adstringens. The bark of this tree is used as a source of medicinal tannin. Harvesting bark, however, often kills the tree. In a manipulative field experiment, we tested the hypothesis that harvesting leaves, which might serve as an alternative source of tannin, would be less detrimental for tree survival, growth, reproduction, and defense than harvesting bark. In a two-way crossed experimental design, we either clipped 100% of a plant’s leaves or applied NPK fertilizer to the soil. Our predictions of the experimental outcomes were based on plant resource and defense theory. Growth was determined by total leaf dry mass production, reproduction by inflorescence and fruit production traits, and defense by total phenolics, hydrolyzable tannins, and condensed tannins. Fertilization had a marginally positive effect on total leaf dry mass. Defoliation had no effect on subsequent leaf production, and most importantly, no plants died as a result of defoliation. We found high tannin amounts in leaves of S. adstringens produced both prior to and subsequent to clipping, further suggesting that leaves could serve as a sustainable alternative source of tannin. After clipping, plants invested more in tannin production and less in reproduction. Our results suggest that leaf harvest may be more sustainable than harvesting of bark in S. adstringens. We suggest the need for further investigation of the medicinal properties of leaf tannins to formulate a viable sustainable management plan for the exploitation of this plant species.