Background: Lifestyle remains a huge driving force of Cardiovascular Diseases (CVD) on-set/progression. Lifestyle-patterns are highly dependent on gender-related attitudes. Objective: To evaluate the gender-specific association of lifestyle-related factors (adherence to Mediterranean diet (MedDiet), Physical Activity (PA), smoking) with 10-year first and recurrent CVD events. Methods: Two prospective studies, the ATTICA (2002-2012, n=3,042 subjects free-of-CVD) and GREECS (2004-2014, n=2,172 subjects with Acute Coronary Syndrome (ACS)) were undertaken. Baseline adherence to MedDiet (MedDietScore <27/≥27, range 0-55), PA (sedentary/physically active) and smoking (current/never) was tested against 10-year first (ATTICA) and recurrent (GREECS) CVD events, in men and women. Results: The “superiority” of men over women regarding overall CVD events was revealed in both first (ATTICA, 19.7% men vs. 11.7% women, p<0.001) and recurrent CVD events, but less significantly (GREECS, 38.8% men vs. 32.9% women, p=0.016). Gender-stratified analysis revealed that: lower adherence to MedDiet in women (Odds Ratio (OR)=1.22, 95% Confidence Interval (95%CI) 1.03, 1.51) and PA (OR=1.35, 95%CI 1.01, 1.85) and smoking (OR=1.28, 95%CI 1.04, 1.82) in men, were independent predictors of 10-year first CVD event; whereas, adherence to MedDiet (OR=1.28, 95%CI 1.01, 1.59), PA (OR=1.25, 95%CI 1.01, 2.50) and smoking (OR=1.15, 95%CI 1.01, 1.30) in women, yet only adherence to MedDiet (OR=1.27, 95%CI 1.01, 1.35) and PA (OR=1.27, 95%CI 1.02, 1.59) in men, were independent predictors of 10-year CVD recurrent events. Conclusion: Differences between men and women, in the effect-size measures of lifestyle-related factors, underline different paths for men and women, probably contributing to better designing strategies for primary and secondary CVD prevention.