Introduction: Greater adherence to a Mediterranean diet is linked to lower risk for cardiovascular morbidity/mortality in studies of Mediterranean cohorts, older subjects, and/or those with existing health conditions. No studies have examined the effects of this dietary pattern in younger working populations in the United States. We investigated the effects of Mediterranean diet adherence on cardiovascular disease (CVD) biomarkers, metabolic syndrome and body composition in an occupationally active, non-Mediterranean cohort. Methods: A cross-sectional study in a cohort of 780 career male firefighters, ages 18 years or older, from the United States Midwest. No dietary intervention was performed. A modified Mediterranean diet score (mMDS) was developed for assessment of adherence to a Mediterranean dietary pattern from a previously administered life-style questionnaire that examined pre-existing dietary habits. Clinical data from fire department medical examinations were extracted and analyzed. Results: Obese subjects had significantly lower mMDS, and they reported greater fast/take-out food consumption (p<0.001) and intake of sweetened drinks during meals (p = 0.002). After multivariate adjustment, higher mMDS was inversely related to risk of weight gain over the past 5 years (odds ratio [OR]: 0.57, 95% confidence interval [CI]: 0.39β0.84, p for trend across score quartiles: 0.01); as well as the presence of metabolic syndrome components (OR: 0.65, 95% CI: 0.44β0.94, p for trend across score quartiles: 0.04). Higher HDL-cholesterol (p = 0.008) and lower LDL-cholesterol (p = 0.04) were observed in those with higher mMDS in linear regression after multivariate adjustment for age, BMI and physical activity. Conclusions: In a cohort of young and active US adults, greater adherence to a Mediterranean-style dietary pattern had significant inverse associations with metabolic syndrome, LDL-cholesterol and reported weight gain, and was significantly and independently associated with higher HDL-cholesterol. Our results support the potential effectiveness of this diet in young, non-Mediterranean working cohorts, and justify future intervention studies