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The aim of this study was to assess the general and sexual health of long-haul truck drivers in the United States.Drivers were recruited from company sites and truck stops in North Carolina, Tennessee, and Mississippi. A sample of 266 drivers was assessed for lifestyle activities; body mass index and blood pressure were measured, and biologic samples were taken for cholesterol, diabetes, and sexually transmitted infection (STI)/HIV testing.The drivers in this study had higher levels of cholesterol and higher rates of smoking, obesity, and diabetes than the U.S average. STI/HIV infection rates were lower than the U.S. average.Long-haul truck driving is a stressful occupation with few opportunities for healthy living. Stress reduction, wellness programs, and better food and exercise options at truck stops should be adopted for the benefit of truckers and the safety of the driving public.