The health benefits of plant-based diets have been reported. Plant-based diets found in Spain and other Mediterranean countries differ from typical diets in other countries. In the Mediterranean diet, a high intake of phenolic compounds through olives, olive oil, and red wine may play an important role in cardiovascular prevention. Prospective studies carried out in Mediterranean countries may provide interesting insights. A relatively young Mediterranean cohort of 16,147 Spanish participants free of cardiovascular disease (CVD) was followed (61% women, mean (SD) age 37(12) years at baseline) for a median of 12.2 years. Dietary intake was repeatedly assessed using a 136-item validated food frequency questionnaire, and (poly)phenol intake was obtained using the Phenol-Explorer database. Participants were classified as incident cases of CVD if a medical diagnosis of myocardial infarction, stroke, or cardiovascular death was medically confirmed. Time-dependent Cox regression models were used to assess the relationship between (poly)phenol intake and the incidence of major CVD. A suboptimal intake of phenolic compounds was independently associated with a higher risk of CVD, multivariable-adjusted hazard ratio for the lowest versus top 4 quintiles: 1.85 (95% CI: 1.09-3.16). A moderate-to-high dietary intake of phenolic compounds, especially flavonoids, is likely to reduce CVD incidence in the context of a Mediterranean dietary pattern.