Autophagy is a major protective mechanism and has been identified in response to hypoxia and more recently, myocardial ischemia, but it is not known whether it is involved in mediating ischemic preconditioning, the most powerful intervention known to protect myocardium against lethal ischemic injury. We examined autophagy in several models of preconditioning induced by six repetitive episodes of ischemia every 12 hours versus classical first or second-window preconditioning in swine. The results indicated that autophagy is an important mechanism mediating cardioprotection following repetitive episodes of coronary stenosis or coronary occlusion, but less for traditional first or second window preconditioning.