AbstractObjective: Past research efforts to determine the influence of the diet on cardiovascular (CV) health have focused on the individual roles of specific dietary components with debatable success. Awareness of the impact and complexity of nutrient interactions has expanded in recent years to include assessment of dietary patterns as they contribute to lower CV disease risk.Research Methods and Procedures: In a series of multicenter studies, we compared a comprehensive, prepared meal plan, formulated to meet recommended intake levels of macro‐ and micronutrients, with a self‐selected diet based on the exchange system. The three studies comprised adult participants with hypertension, hyperlipidemia, and type 2 diabetes (n = 560, 251, and 330, respectively). The first two studies (10 weeks) varied by the amount of contact with study personnel, and the third study assessed long‐term effects over 52 weeks. Outcome measures included: blood pressure, lipid and lipoprotein levels, glycemic control, homocysteine, compliance, quality of life, and weight.Results: The first study demonstrated significant improvements in all measures, with greater improvements with the prepared meal plan compared with the self‐selected diet. The second study, designed to parallel the contact frequency that would occur in a real world clinical setting, also produced significant improvements in multiple CV risk factors. In the long‐term study, in addition to sustained improvements in risk factors, significant weight loss was achieved and maintained over the 52 weeks.Discussion: These trials demonstrate that regular consumption of a nutritionally complete diet offers multiple, concurrent clinical benefits for reducing CV disease risk and body weight.