Background: While maintenance of a low cardiovascular risk profile is essential for cardiovascular disease (CVD) prevention, few people maintain a low CVD risk profile throughout their life. We studied the association of demographic, lifestyle, psychological factors and family history of CVD with attainment and maintenance of a low risk profile over three subsequent 5-year periods. Methods: Measurements of 6390 adults aged 26-65 years at baseline were completed from 1993 to 97 and subsequently at 5-year intervals until 2013. At each wave, participants were categorized into low risk profile (ideal levels of blood pressure, cholesterol and body mass index, non-smoking and no diabetes) and medium/high risk profile (all others). Multivariable-adjusted modified Poisson regression analyses were used to examine determinants of attainment and maintenance of low risk; risk ratios (RR) and 95% confidence intervals (95% CI) were obtained. Generalized estimating equations were used to combine multiple 5-year comparisons. Results: Younger age, female gender and high educational level were associated with higher likelihood of both maintaining and attaining low risk profile (P < 0.05). In addition, likelihood of attaining low risk was 9% higher with each 1-unit increment in Mediterranean diet score (RR: 1.09, 95% CI: 1.02-1.16), twice as high with any physical activity versus none (RR: 2.17, 95% CI: 1.16-4.04) and 35% higher with moderate alcohol consumption versus heavy consumption (RR: 1.35, 95% CI: 1.06-1.73). Conclusion: Healthy lifestyle factors such as adherence to a Mediterranean diet, physical activity and moderate as opposed to heavy alcohol consumption were associated with a higher likelihood of attaining a low risk profile.