BACKGROUND: Cardiovascular disease (CVD) is a major economic burden in the United States. CVD risk factors, particularly hypertension and hypercholesterolemia, are typically treated with drug therapy. Five-year efficacy of such drugs to prevent CVD is estimated to be 5%. Plant-based diets have emerged as effective mitigators of these risk factors. HYPOTHESIS: The implementation of a defined, plant-based diet for 4 weeks in an outpatient clinical setting may mitigate CVD risk factors and reduce patient drug burden. METHODS: Participants consumed a plant-based diet consisting of foods prepared in a defined method in accordance with a food-classification system. Participants consumed raw fruits, vegetables, seeds, and avocado. All animal products were excluded from the diet. Participant anthropometric and hemodynamic data were obtained weekly for 4 weeks. Laboratory biomarkers were collected at baseline and at 4 weeks. Medication needs were assessed weekly. Data were analyzed using paired-samples t tests and 1-way repeated-measures ANOVA. RESULTS: Significant reductions were observed for systolic (-16.6 mmHg) and diastolic (-9.1 mmHg) blood pressure (P < 0.0005), serum lipids (P ≤ 0.008), and total medication usage (P < 0.0005). Other CVD risk factors, including weight (P < 0.0005), waist circumference (P < 0.0005), heart rate (P = 0.018), insulin (P < 0.0005), glycated hemoglobin (P = 0.002), and high-sensitivity C-reactive protein (P = 0.001) were also reduced. CONCLUSION: A defined, plant-based diet can be used as an effective therapeutic strategy in the clinical setting to mitigate cardiovascular risk factors and reduce patient drug burden.