Esselstyn became an advocate of a plant-strong diet in the 1970s, when he directed the American Cancer Society’s nutrition education program, Cancer Prevention Program. During this time, he was also a member of the Nutrition Advisory Board of the American Heart Association, and he served as the nutrition advisor to the U.S. Olympic Committee from 1973 until 1979. In the 1980s, he helped to establish the U.S. Department of Agriculture’s nutrition education programs. He is the recipient of numerous honors, including membership in the American Association for the Advancement of Science, the Institute of Medicine, the National Academy of Sciences and the National Cancer Institute. He has also received the Omega-3 International Award, the International Federation of Nutrition Societies’ Lifetime Achievement Award, the Linus Pauling Award and the French Academy of Nutrition’s Nutrition Award. He received the Guy Trigault Memorial Award for his work in cancer prevention in 2003.
In 2013, Esselstyn was interviewed for the documentary film In Defense of Food by Michael Pollan, author of The Omnivore's Dilemma (2007), which addresses the idea that a plant-based diet is healthier than one that includes animal products. In the interview, Esselstyn discusses the origins of Engine 2, he looks at the impact of the diet on firefighter health, and he discusses the ethics of the diet. It was released in theaters on August 2, 2013. In early 2015, he was interviewed for the Netflix series The Mind of a Chef about health and nutrition.
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