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Background Adherence to the Mediterranean diet reduces the risk of all-cause and cardiovascular (CV) mortality and the incidence of CV events. However, most previous studies were performed in high-risk individuals. Our objective was to assess whether the adherence to the Mediterranean diet, evaluated by the MED score, was associated with all-cause and CV mortality and incidence of CV events in individuals at low CV risk from a population-based cohort, after a 12-year mean follow-up. Methods A cohort of 1658 individuals completed a validated food-frequency questionnaire in 2001–2003. The MED score was calculated by a 0–9 scale. Anthropometric, laboratory measurements, and the vital status were collected at baseline and during 2014. The baseline CV risk was estimated by the Framingham risk score. Participants were divided into two groups: individuals at low risk (CV 6) individuals. Values of BMI, waist circumference, fasting glucose and insulin significantly decreased from low to high diet adherence only in participants with CV risk ≥10. In a Cox-regression model, the hazard ratios (HRs) in low-risk individuals per unit of MED score were: HR = 0.83 (95 % CI 0.72–0.96) for all-cause mortality, HR = 0.75 (95 % CI 0.58–0.96) for CV mortality, and HR = 0.79 (95 % CI 0.65–0.97) for CV events, after multiple adjustments. In individuals with CV risk ≥10, the MED score predicted incident CV events (HR = 0.85; 95 % CI 0.72–0.99), while the associations with all-cause (HR = 1.02; 95 % CI 0.90–1.15) and CV mortality (0.94; 95 % CI 0.76–1.15) were not significant. Conclusions Greater adherence to the Mediterranean diet was associated with reduced fatal and non fatal CV events, especially in individuals at low CV risk, thus suggesting the usefulness of promoting this nutritional pattern in particular in healthier individuals.