In order to assess the effectiveness of lifestyle interventions in reducing cardiovascular disease risk factors, morbidity and mortality among working-age adults, we undertook a systematic review of randomized controlled trials of various lifestyle interventions (diet, exercise, smoking cessation, alcohol intake reduction) in adults followed for 1 year or longer. Twenty-one single-factor and 21 multifactorial interventions were analysed by outcome. Changes in cardiovascular morbidity and mortality and total mortality were considered as main outcomes. Changes in weight, total cholesterol, blood pressure, sodium excretion, smoking and alcohol consumption were also analysed, and numbers needed to treat were calculated for smoking, morbidity and mortality. In secondary prevention, both single and multifactorial lifestyle interventions were shown to reduce morbidity and mortality, and multifactorial approaches reduced cholesterol levels. Primary prevention was found to reduce risk factors efficiently, especially when the intervention is multifactorial. Effect sizes were heterogeneous with wide confidence intervals. Standardized ways of describing interventions, measuring their effects and reporting outcomes systematically would facilitate effect-size evaluations. Interventions should optimally be multifactorial and targeted at high-risk patients with multiple risk factors for cardiovascular disease.