Background-Secondary prevention by risk factor modification improves patient outcomes, yet it is often not achieved in clinical practice. Reasons for failure stem from challenges of prioritizing risk factor reduction and engaging patients in changing their behaviors. We hypothesize that a novel telemedicine intervention with tailored patient education could improve cardiovascular risk factors. Methods-To evaluate this intervention, we propose enrolling 450 patients with a recent myocardial infarction and hypertension into a 3-arm randomized, controlled trial. The first arm (nϭ150) will receive home blood pressure (BP) monitors plus a nurse-delivered, telephone-based tailored patient education intervention and will be enrolled into HealthVault, a Microsoft electronic health record platform. The second arm (nϭ150) will also receive BP monitors plus a tailored patient education intervention and be enrolled in HeartVault. However, the patient education intervention will be delivered by a Web-based program and will cover topics identical to those in the nurse-delivered intervention. Both arms will be compared with a control group receiving standard care (nϭ150). All participants will have an in-person assessment at baseline and at completion of the study, including standardized measurements of BP, LDL cholesterol, and glycosylated hemoglobin (in diabetic subjects). The study design will allow assessment of a telephone-based, nurse-administered disease management program versus standard care. The main outcome of interest is the reduction in systolic BP in each intervention group compared with the control group at 12 months. Secondary outcomes assessed will include reductions in LDL cholesterol, body weight, and glycosylated hemoglobin, as well as adherence to evidence-based therapies and improvement in health behaviors. Conclusion-If successful in optimizing BP control, managing other coronary heart disease risk factors, and demonstrating a lower cost, the Web-based disease management tool has the potential to enhance coronary artery disease management, quality of care, and ultimately, patient outcomes. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901277. (Circ Cardiovasc Qual Outcomes. 2011;4:235-242.)