Open access. Cardiovascular disease is the leading cause of the estimated 11–25 years reduced life expectancy for persons with serious mental illness (SMI). This excess cardiovascular mortality is primarily attributable to obesity, diabetes, hypertension, and dyslipidaemia. Obesity is associated with a sedentary lifestyle, limited physical activity and an unhealthy diet. Lifestyle interventions for persons with SMI seem promising in reducing weight and cardiovascular risk. The aim of this study is to evaluate the effectiveness and cost-effectiveness of a lifestyle intervention among persons with SMI in an outpatient treatment setting.