Although cardiovascular disease (CVD) and diabetes mellitus are largely lifestyle driven, lifestyle metrics are not used in clinical practice. This study examined the relevance of using a simple lifestyle risk score designed for primary care medicine by testing its ability to predict biological CVD risk factors in a cohort of 3,712 individuals involved in a workplace health evaluation or management program (“Grand Défi Entreprise” project). Using a lifestyle risk score based on waist circumference, fitness, nutritional quality, and physical activity level, employees were categorized into 3 distinct estimated lifestyle risk levels (low, intermediate, and high). A biological CVD risk score was also calculated, which included high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), cholesterol-to-HDL-C ratio, blood pressure, hemoglobin glycated levels, and medication use. Diastolic blood pressure, TG levels, and the cholesterol-to-HDL-C ratio increased across categories of lifestyle risk score, whereas HDL-C decreased (p <0.05). Calculated Framingham and diabetes risk scores as well as the prevalence of hypertriglyceridemic waist phenotype also increased across categories of lifestyle risk score (p <0.05). Finally, 1-way analysis of variance revealed that the biological risk score significantly increased across the lifestyle risk score categories (p <0.0001). Our study provides evidence that lifestyle variables can be measured and targeted in clinical practice.