ABSTRACT: Despite well-publicized guidelines on the appropriate management of cardiovascular disease and type 2 diabetes, the implementation of risk-reducing practices remains poor. This report describes the results of a randomized, controlled clinical trial evaluating the effectiveness of a comprehensive program of cardiovascular disease risk reduction delivered by nurse practitioner /community health worker (NP/CHW) teams versus enhanced usual care (EUC) to improve lipids, blood pressure, glycated hemoglobin (HbA1c), and patient perceptions of the quality of their chronic illness care in patients in urban community health centers.A total of 525 patients with documented cardiovascular disease, type 2 diabetes, hypercholesterolemia, or hypertension and levels of LDL cholesterol, blood pressure, or HbA1c that exceeded goals established by national guidelines were randomly assigned to NP/CHW (n=261) or EUC (n=264) groups. The NP/CHW intervention included aggressive pharmacological management and tailored educational and behavioral counseling for lifestyle modification and problem solving to address barriers to adherence and control. Compared with EUC, patients in the NP/CHW group had significantly greater 12-month improvement in total cholesterol (difference, 19.7 mg/dL), LDL cholesterol (difference,15.9 mg/dL), triglycerides (difference, 16.3 mg/dL), systolic blood pressure (difference, 6.2 mm Hg), diastolic blood pressure (difference, 3.1 mm Hg), HbA1c (difference, 0.5%), and perceptions of the quality of their chronic illness care (difference, 1.2 points).An intervention delivered by an NP/CHW team using individualized treatment regimens based on treat-to-target algorithms can be an effective approach to improve risk factor status and perceptions of chronic illness care in high-risk patients.