Background: Cardiovascular prevention guidelines promote a healthy lifestyle and the management of risk factors to reduce cardiovascular risk. The impact of adherence to these guidelines on overall and cardiovascular mortality is not well understood. The impact of adherence to the 2016 European Society of Cardiology guidelines on all-cause and cardiovascular mortality was assessed in a representative sample of the French population. Methods: The analysis was based on the third population survey of the Monica project, conducted from 1994 to 1997. A score of adherence to European guidelines was created, based on adherence to recommendations regarding: smoking, alcohol consumption, physical activity, body mass index, blood pressure, LDL cholesterol, HDL cholesterol, fasting blood glucose, and nutrition. Vital status was obtained 18 years after enrollment. The statistical analysis is based on a multivariate Cox model. Results: The adherence score was assessed in 1,311 healthy subjects aged 35 to 64 years (73% men). During follow-up, 186 deaths were recorded (41 deaths from cardiovascular causes). For cardiovascular mortality, the adjusted relative risk for subjects in the 4th adherence quartile (those with the lowest adherence) was 3.12 [1.62–6.01] (p=0.001), compared to subjects in the 1st, 2nd, and 3rd quartiles (those with the highest adherence). For all-cause mortality, the adjusted relative risk for subjects in the 4th quartile of adherence was 2.27 [1.68–3.06] (p<0.001). Conclusions: Better adherence to European cardiovascular prevention guidelines is associated with lower long-term cardiovascular and all-cause mortality in the general French population.