Few data exist on the effectiveness of cardiovascular disease (CVD) risk-reduction programs in patients with limited access to health care. The objective of this project was to evaluate a disease management approach to multifactor CVD risk reduction in patients with limited or no health insurance and low family income. Patients (n = 148) were recruited from not-for-profit or free clinics and hospitals and randomized to usual care or usual care plus team case management. Mean age was 59.3 years, 57% were women, 50% had less than a high school education, 57% were Hispanic, and 64% had no health insurance. All had ≥1 increased risk factor for CVD, and 24.5% had documented coronary artery disease. Follow-up measurements were obtained at 6 and 12 months. Primary outcomes were low-density lipoprotein cholesterol and systolic blood pressure. The disease management program was supervised by a physician, delivered by nurses and dietitians, and included comprehensive lifestyle changes and medications. Data were collected on 91% of patients at 12 months. Disease management produced clinically important decreases in selected risk factors compared with usual care, including systolic blood pressure (p <0.01) and low-density lipoprotein cholesterol (p <0.03). More patients with disease management than those with usual care moved from “high” and “very-high” risk to lower risk categories for selected risk factors. In conclusion, the disease management program had excellent retention and lower CVD risk factors and demonstrated the potential of such approaches for decreasing long-term disease burden in selected medically underserved populations.