Cardiovascular disease mortality rates have begun to rise in the United States. Based on the large body of supportive evidence, we propose a proof-of-concept, first-in-human trial to cure atherosclerosis: CURing Early ATHEROsclerosis (CURE ATHERO). This trial is based on a model of intensive induction therapy for extensive, if not complete, plaque regression, followed by intermittent maintenance therapy. An extensive body of evidence has demonstrated the causal role of apolipoprotein B lipoproteins in atherosclerosis progression and data suggest intensive low-density lipoprotein cholesterol (LDL-C) lowering may have a substantial impact on earlier stages of atherosclerosis. Compared with lifetime treatment to prevent atherosclerosis progression, this induction–intermittent treatment model will minimize costs and maximize adherence and safety.