Introduction: Cardiovascular disease (CVD) is the leading cause of death in the United States for middle-aged men and women despite the fact that prevention and control of CVD is achievable by modifying risk factors through lifestyle changes and diet therapy. We examined the impact of four diet programs (plant-based (Vegan), Mediterranean, Paleolithic (Paleo) and DASH diets) on the CV risk factor profile of adults in the Hampton Roads area of Virginia. Hypothesis: Among the Diets studies, there will be a variable response with regards to impact on lipids. Methods: Nondiabetic adults (ages 35-85) with one or more risk factors for CVD were invited to participate in 1 of the 4 diet arms. Participants underwent a comprehensive nutrition education program prior to a 60-day diet intervention in which they kept a daily food log and met weekly with a multi-disciplinary study team. An initial health screen was performed to assess weight, blood pressure (BP), fasting glucose (FPG), A1C, lipids and lipoprotein particles, and repeated after 60 days on the diet and at 6-months follow-up. Results: 279 subjects completed the 60-day dietary intervention (58 Vegan, 80 Mediterranean, 76 Paleo, 65 DASH), and 199 returned for 6-month follow-up. Most subjects were female, Caucasian, mean age 56, mean BMI 33 kg/m2. At baseline, mean FPG, TG and HDL-C were within the normal range, whereas LDL-P and BP were elevated. After 60 days on the respective diets, subjects lost an average of 9 lbs (4.7% body weight, total 2,576 lbs), which was associated with improvements in BP across all groups. Subjects on the Vegan and Paleo diets lost the most weight (~6.5%) and showed the greatest improvement in lipid risk factors (11-14% decrease in LDL-P; 10-20% decrease in VLDL and TG). Conclusions: All four diets promoted weight loss and improved BP but had variable effects on lipid risk factors.