BACKGROUND: Evidence on the prospective relationship between cardiovascular health (CVH) and chronic obstructive pulmonary disease (COPD) risk is limited, particularly regarding genetic susceptibility as an effect modifier. OBJECTIVES: We aimed to investigate the association between CVH levels and COPD risk and to determine whether genetic susceptibility influences this relationship. METHODS: We included 293,342 participants free of COPD from the UK Biobank cohort. CVH levels were assessed using the Life's Essential 8 (LE8) and the Life's Simple 7 scores. Genetic predisposition to COPD was quantified via the polygenic risk score. Cox proportional hazard models examined the impacts of CVH levels and polygenic risk score on COPD incidence. RESULTS: During a median follow-up of 12.89 (Q1-Q3: 12.22-13.54) years, 9,481 participants developed COPD, with an incidence rate of 2.533 per 1,000 person-years (95% CI: 2.482-2.584). Compared to low CVH levels measured by LE8, the HRs (95% CI) for incident COPD were 0.468 (0.446-0.490) for moderate and 0.201 (0.177-0.227) for high CVH levels. No statistically significant interactions were observed between CVH levels and genetic susceptibility to COPD. LE8 showed better predictive accuracy for COPD incidence than Life's Simple 7, with a higher area under the receiver operating characteristic curve (0.698 [95% CI: 0.693-0.704] vs 0.677 [95% CI: 0.672-0.682], P < 0.001). CONCLUSIONS: High CVH levels are significantly associated with a lower risk of incident COPD, regardless of genetic predisposition. These findings highlight the importance of maintaining optimal CVH in COPD prevention. (Predictors of coronary artery calcification [CAC] progression in the UKB population; 91090).