We conducted this systematic review to support the U.S. Preventive Services Task Force (USPSTF) in updating its 2012 recommendation on behavioral counseling to promote a healthful diet and physical activity for the primary prevention of cardiovascular disease (CVD) in adults without known CVD risk factors. Our review addressed four key questions: 1) Do primary care behavioral counseling interventions to improve diet, increase physical activity, and/or reduce sedentary behavior improve health outcomes in adults? 2) Do primary care behavioral counseling interventions to improve diet, increase physical activity, and/or reduce sedentary behavior improve intermediate outcomes associated with CVD in adults? 3) Do primary care behavioral counseling interventions to improve diet, increase physical activity, and/or reduce sedentary behavior improve associated health behaviors in adults? 4) What adverse events are associated with primary care behavioral counseling interventions to improve diet, increase physical activity, and/or reduce sedentary behavior in adults?