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Though smoking cessation is the best way to reduce premature death among individuals who have cardiovascular diseases (CVD), a substantial percentage of individuals with these conditions continue to smoke. Given well-known associations between disadvantaged environments and smoking, we investigate life-course pathways from early-life adversities (ELAs) to risk of recalcitrant smoking in midlife. Using longitudinal data from Midlife in the U.S., respondents were categorized into five groups: non-smokers, ex-smokers without CVD, ex-smokers with CVD, current smokers without CVD, current smokers with CVD (recalcitrant smokers). ELAs includes low childhood SES, family instability, and abuse that represent economic hardships and abusive/insecure relationships in childhood. We found that ELAs are significantly associated with elevated likelihood of being recalcitrant smokers, but the unique effect of each ELA varies by gender. The risk of being recalcitrant smokers increases for women who experienced family instability and for men who experienced low childhood SES. These ELA effects were robust for both genders, even after accounting for life-course mediators. There are life-course factors that significantly differentiate recalcitrant smokers from ex-smokers with CVD: for women, having poor education and not living with a partner while for men having family problems and low purpose in life. Our findings expand the current understanding of childhood as a critical period that contributes to the persistence of health-risk behaviors in later life. The findings also underscore the need to develop gender-specific interventions to reduce such an intractable smoking habit.