"Optimal lifestyle," comprising abstinence from smoking, adequate physical activity, eating 5 servings of fruits and vegetables each day, and consuming limited or no alcohol, is associated with low risk of chronic disease when unselected populations are observed for long periods of time. It is unclear whether these same associations are present when observation is limited to employed individuals followed for a brief period of time. The purpose of this investigation was to study the association between adherence to optimal lifestyle and the incidence of chronic conditions among employees over a 2-year period. Logistic regression was used to assess the association between employees' (N = 6848) adherence to optimal lifestyle and the incidence of diabetes, heart disease, cancer, hypertension, high cholesterol, and back pain during a 2-year period. All data were self-reported. Adherence to any 3 components of the optimal lifestyle was associated with a significantly lower near-term incidence of diabetes (odds ratio [OR] = 0.56; 95% confidence interval [CI] = 0.31-0.97) and back pain (OR = 0.69; 95% CI = 0.53-0.92). Adherence to all 4 optimal lifestyle components was significantly associated with lower near-term incidence of back pain (OR = 0.44; 95% CI = 0.26-0.76). Physical activity was associated with significantly lower near-term incidence risk of heart disease (OR = 0.60; 95% CI = 0.38-0.95), high cholesterol (OR = 0.80; 95% CI = 0.66-0.99), and diabetes (OR = 0.51; 95% CI = 0.30-0.86). Adherence to optimal lifestyle, in particular adequate physical activity, is associated with lower near-term risk of developing several chronic conditions. Employers and payers should consider this fact when formulating policy or allocating resources for health care and health promotion.