Research is needed to validate effective and practical strategies for improving the provision of evidence-based medicine in primary care. To determine whether a multimethod quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators for primary and secondary prevention of cardiovascular disease and stroke. 2-year randomized, controlled clinical trial with the practice as the unit of randomization. 20 community-based family or general internal medicine practices in 14 states. All used the same electronic medical record. 44 physicians, 17 midlevel providers, and approximately 200 staff members; data from the electronic medical records of 87,291 patients. All practices received copies of practice guidelines and quarterly performance reports. Intervention practices also hosted quarterly site visits to help them adopt quality improvement approaches and participated in 2 network meetings to share "best practice" approaches. The percentage of indicators at or above predefined targets and the percentage of patients who had achieved each clinical indicator. Intervention practices improved 22.4 percentage points (from 11.3% to 33.7%) in the percentage of indicators at or above the target; control practices improved 16.4 percentage points (from 6.3% to 22.7%). The 6.0-percentage point absolute difference between the intervention and control group was not statistically significant (P > 0.2). Patients in intervention practices had greater improvements than those in control practices for diagnoses of hypertension (improvement difference, 15.7 percentage points 95% CI, 5.2 to 26.3 percentage points) and blood pressure control in patients with hypertension (improvement difference, 8.0 percentage points CI, 0.0 to 16.0 percentage points). The study involved a small number of practices and lacked a pure control group. Primary care practices that use electronic medical records and receive regular performance reports can improve their adherence to clinical practice guidelines for cardiovascular disease and stroke prevention.