CONTEXT: Clinical decision support systems (CDSSs) can help clinicians assess cardiovascular disease (CVD) risk and manage CVD risk factors by providing tailored assessments and treatment recommendations based on individual patient data. The goal of this systematic review was to examine the effectiveness of CDSSs in improving screening for CVD risk factors, practices for CVD-related preventive care services such as clinical tests and prescribed treatments, and management of CVD risk factors. EVIDENCE ACQUISITION: An existing systematic review (search period, January 1975-January 2011) of CDSSs for any condition was initially identified. Studies of CDSSs that focused on CVD prevention in that review were combined with studies identified through an updated search (January 2011-October 2012). Data analysis was conducted in 2013. EVIDENCE SYNTHESIS: A total of 45 studies qualified for inclusion in the review. Improvements were seen for recommended screening and other preventive care services completed by clinicians, recommended clinical tests completed by clinicians, and recommended treatments prescribed by clinicians (median increases of 3.8, 4.0, and 2.0 percentage points, respectively). Results were inconsistent for changes in CVD risk factors such as systolic and diastolic blood pressure, total and low-density lipoprotein cholesterol, and hemoglobin A1C levels. CONCLUSIONS: CDSSs are effective in improving clinician practices related to screening and other preventive care services, clinical tests, and treatments. However, more evidence is needed from implementation of CDSSs within the broad context of comprehensive service delivery aimed at reducing CVD risk and CVD-related morbidity and mortality.