Dr. Esselstyn has been associated with the Cleveland Clinic since 1968. In 1991, he served as President of the American Association of Endocrine Surgeons. That same year he organized the first National Conference on the Elimination of Coronary Artery Disease. In 1995 he published his bench mark long-term nutritional research arresting and reversing coronary artery disease in severely ill patients. That same study was updated at 12 years and reviewed beyond twenty years in his book, Prevent and Reverse Heart Disease, making it one of the longest longitudinal studies of its type. In July of 2014 he reported the experience of 198 participants seriously ill with cardiovascular disease. During 3.7 years of follow up of the 89% adherent to the program, 99.4% avoided further major cardiac events. Among many other awards, he received the American College of Lifestyle Medicine 2016 Lifetime Achievement Award.

Dr. Esselstyn and his wife, Ann Crile Esselstyn, have followed a plant-based diet since 1984. Dr. Esselstyn presently directs the cardiovascular prevention and reversal program at The Cleveland Clinic Wellness Institute.