Most Americans do not meet diet and physical activity recommendations despite known health benefits. To systematically review the benefits and harms of lifestyle counseling interventions in persons with cardiovascular risk factors for the U.S. Preventive Services Task Force. MEDLINE, PsycINFO, the Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials (January 2001 to October 2013); experts; and existing systematic reviews. Two investigators independently reviewed 7218 abstracts and 553 articles against a set of inclusion and quality criteria. Data from 74 trials were abstracted by one reviewer and checked by a second. At 12 to 24 months, intensive lifestyle counseling in persons selected for risk factors reduced total cholesterol levels by an average of 0.12 mmol/L (95% CI, 0.16 to 0.07 mmol/L) (4.48 mg/dL CI, 6.36 to 2.59 mg/dL), low-density lipoprotein cholesterol levels by 0.09 mmol/L (CI, 0.14 to 0.04 mmol/L) (3.43 mg/dL CI, 5.37 to 1.49 mg/dL), systolic blood pressure by 2.03 mm Hg (CI, 2.91 to 1.15 mm Hg), diastolic blood pressure by 1.38 mm Hg (CI, 1.92 to 0.83 mm Hg), fasting glucose levels by 0.12 mmol/L (CI, 0.18 to 0.05 mmol/L) (2.08 mg/dL CI, 3.29 to 0.88 mg/dL), diabetes incidence by a relative risk of 0.58 (CI, 0.37 to 0.89), and weight outcomes by a standardized mean difference of 0.25 (CI, 0.35 to 0.16). Behavioral changes in dietary intake and physical activity were generally concordant with changes in physiologic outcomes. Sparse reporting of patient health outcomes, longer-term follow-up of outcomes, and harms. Intensive diet and physical activity behavioral counseling in persons with risk factors for cardiovascular disease resulted in consistent improvements across various important intermediate health outcomes up to 2 years. Agency for Healthcare Research and Quality.