Background: Epidemiological and experimental evidence support a protective effect of dietary polyphenols on chronic diseases, but high quality longitudinal data are needed, including details on categories of polyphenols. Our objective was to investigate the prospective association between total and individual classes and subclasses of dietary polyphenols and the risk of major cardiovascular disease in the NutriNet-Sante cohort. Methods: A total of 84,158 participants, who completed at least three 24 h dietary records, were included between May 2009 and June 2017. Individual polyphenols intakes were obtained by matching food consumption data from the 24 h dietary records with the Phenol-Explorer polyphenol composition database. Multivariable Cox proportional hazards models were used to characterize the associations between dietary polyphenols and the incidence of cardiovascular diseases, comparing tertile T3 vs. T1 of classes and subclasses of polyphenols. Results: Over a median of 4.9 years of follow-up, 602 major cardiovascular events were diagnosed. Intakes of anthocyanins, catechins, and flavonols were strongly inversely associated with cardiovascular disease risk (anthocyanins: Hazard Ratio (HR)(for a 1-point increment of 10 mg/day) = 0.98 (0.96-0.99, p = 0.03, HRT3vs.(T1) = 0.66 (0.52-0.83), p(trend) = 0.0003; catechins: HRfor a 1-point increment of 10 mg/day = 0.98 (0.96-0.99), p = 0.02, HRT3vs. (T1) = 0.74 (0.60-0.91), p(trend) = 0.004; flavonols: HRfor a 1-point increment of 10 mg/day = 0.94 (0.90-0.99), p = 0.02, HRT3vs.(T1) = 0.75 (0.61-0.94), p(trend) = 0.006). Intakes of dihydrochalcones, proanthocyaninidins, dihydroflavonols, hydroxybenzoic acids, and stilbenes were also associated with a decrease (13%, 19%, 24%, 24%, and 27%, respectively) in cardiovascular disease risk, when comparing tertile T3 to T1. Conclusions: Higher intakes of polyphenols, especially of anthocyanins, catechins, and flavonols, were associated with a statistically significant decreased cardiovascular disease risk.