Patients who have had an acute myocardial infarction (MI) are at increased risk of mortality and morbidity. International guidelines agree on the use of combination of the following drugs: platelet antiplatelets, β-blockers, ACEI⁄ARBs and statins. The benefits of chronic polytherapy in reducing cardiovascular disease have been clearly shown. However, observational studies reported poor adherence to chronic polytherapy. We identified about 52,000 patients discharged from hospital with a first MI diagnosis from three Italian regions: Lazio, Toscana and Sicilia. Adherence to chronic poly-therapy in the two years after hospital discharge ranged from 63% in the Lazio region to 27% in the Sicilia region. More than 75 percent of MI patients had chronic concomitant diseases. Chronic diseases played a major role among barriers to adherence. MI patients with multimorbidity have complex health needs but, due to the current traditional disease-oriented approach, they face a highly fragmented form of care that leads to incomplete, inefficient, ineffective and possibly harmful clinical interventions, and are likely to receive complex drug regimens, which increase the risk of inappropriate prescribing, drug-drug interactions, and poor adherence. In order to address patient-specific needs, a network of multidisciplinary teams should be implemented, avoiding fragmentation and ensuring continuity of care.