Cardiac rehabilitation programmes are a proven treatment for individuals with recent myocardial infarction, resulting in reduced morbidity and mortality compared to usual care. Unfortunately, following completion of a cardiac rehabilitation programme, risk factors and lifestyle behaviours may deteriorate. The GlObal Secondary Prevention strategiEs to Limit event recurrence after myocardial infarction (GOSPEL) study investigates the benefits of a programme of continued educational and behavioural interventions to achieve optimal long-term secondary prevention goals. This will be a multicentre, randomized, controlled study carried out in 78 Italian cardiac rehabilitation centres. After completion of an initial cardiac rehabilitation programme, patients with recent (<3 months) myocardial infarction were randomized to either a long-lasting (over 3 years) multifactorial continued educational and behavioural programme (intensive approach) or usual care (control) group. Intensive approach patients participated in extensive cardiac rehabilitation sessions, monthly from months 1 to 6, then every 6 months for 3 years. Each session consisted of aerobic exercise, comprehensive lifestyle and risk factor counselling, and clinical assessment. Usual care patients returned to their family physicians' care, and attended the reference centre only for the 6-month and then annual scheduled assessment. The efficacy of the two different strategies will be evaluated in terms of morbidity and mortality as primary endpoint. From January 2001 through December 2002, 3241 patients were enrolled. Results will be available in mid 2006. The GOSPEL trial, the rationale and design of which we present here, was designed to test a new strategy of secondary prevention delivery and to raise standards of long-term secondary prevention in Italy. With a cohort of over 3200 patients, GOSPEL is the largest randomized, multifactorial lifestyle and risk factor intervention trial after myocardial infarction conducted so far.