ABSTRACT: The protective effect of different healthy lifestyle scores for the risk of cardiovascular disease (CVD) was reported, although the comparisons of performance were lacking. We compared the performance measures of CVDs from different healthy lifestyle scores among Taiwanese adults. We conducted a nationwide prospective cohort study of 6042 participants (median age 43 years, 50.2% women) in Taiwan’s Hypertensive, Hyperglycemia and Hyperlipidemia Survey, of whom 2002 were free of CVD at baseline. The simple and weighted the Mediterranean diet related healthy lifestyle (MHL) scores were defined as a combination of normal body mass index, Mediterranean diet, adequate physical activity, non-smokers, regular healthy drinking, and each dichotomous lifestyle factor. The World Cancer Research Fund and American Institute for Cancer Research cancer prevention recommended lifestyle and Life's Simple 7 following the guideline definition. The incidence of CVD among the four healthy lifestyle scores, each divided into four subgroups, was estimated. During a median 14.3 years follow-up period, 520 cases developed CVD. In the multivariate-adjusted Cox proportional hazard models, adherence to the highest category compared with the lowest one was associated with a lower incidence of CVD events, based on the simple (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.2–0.94) and weighted MHL scores (HR 0.44, 95% CI 0.28–0.68). Additionally, age played a role as a significant effect modifier for the protective effect of the healthy lifestyle scores for CVD risk. Specifically, the performance measures by integrated discriminative improvement showed a significant increase after adding the simple MHL score (integrated discriminative improvement: 0.51, 95% CI 0.16–0.86, P = 0.002) and weighted MHL score (integrated discriminative improvement: 0.38, 95% CI 0.01–0.74, P = 0.021). We demonstrated that the healthy lifestyle scores with an inverse association with CVD and reduced CVD risk were more likely for young adults than for old adults. Further studies to study the mechanism of the role of lifestyle on CVD prevention are warranted.