To test the hypothesis that recovery of myocardial oxidative metabolism (MVO2) is a necessary prerequisite for recovery of contractile function following reperfusion and to evaluate its dependency on the interval of antecedent ischemia before reflow, we evaluated 11 dogs serially for 4 weeks. Six dogs were subjected to prompt reperfusion (after 1 hour of coronary artery occlusion) and five were subjected to delayed reperfusion (after 4 hours of ischemia). Despite equivalent levels of myocardial blood flow with reperfusion, hearts subjected to prompt reperfusion had faster and more complete recovery of MVO2 (assessed by sequential positron emission tomography with [11C]acetate) and function (assessed by echocardiography) compared with dogs subjected to delayed reperfusion. Infarct size was diminished in dogs with prompt reperfusion. In all dogs, recovery of function with reperfusion was predicted and correlated with early recovery of MVO2 (r = 0.61, p < 0.04). The results demonstrate that prompt reperfusion is associated with more rapid and complete recovery of oxidative metabolism and function and support the hypothesis that the ability to metabolize substrate oxidatively is a necessary prerequisite for recovery of function.