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Key Points In general, an inverse relationship between smoking and BMI exists Post-cessation-related obesity might contribute to insulin resistance The number one reason for not wanting to quit smoking or quitting and then relapsing is fear of post-cessation weight gain, especially in women and in individuals with obesity Future smoking cessation programs and therapies need to be designed with an emphasis on reducing post-cessation weight gain The benefits of smoking cessation outweigh the risks Abstract Smoking continues to be the leading cause of preventable death in the USA, despite the vast and widely publicized knowledge about the negative health effects of tobacco smoking