Salicylate is widely used as a stable trap for the highly reactive hydroxyl radical. The purpose of this study was to determine whether the addition of salicylate to hearts subjected to ischemia and reperfusion was able to prevent some injury. Salicylate was able to inhibit mitochondrial damage, and preserved ascorbate and alpha-tocopherol depletion due to ischemia/reperfusion in rat hearts. It did not prevent the elevation of low molecular weight iron. We conclude that salicylate functions as an antioxidant and afforded protection against ischemia and reperfusion.