Aim To investigate the relationship between serum level of periostin and prognosis of patients with acute myocardial infarction (AMI). Methods Serum periostin was measured by using enzyme-linked immunosorbent assay in 178 patients with AMI immediately after hospitalization. All patients were followed up for 12 and 18 months. Major adverse cardiac and cerebrovascular events (MACCE) were counted, including death, stroke/transient ischemic attack, recurrent chest pain, ischemia and re-admission. The relationship between the level of periostin and the prognosis of cardiovascular disease was evaluated. Results Follow-up results showed that MACCE composite end-point in high periostin group of AMI patients was higher than that in low periostin group after 12 months follow-up (P＜0.05). Recurrent chest pain, ischemia and re-admission, and MACCE composite end-point in high periostin group were higher than those in low periostin group after 18 months follow-up (P＜0.05). The results suggested that the serum level of the periostin might be used as an index to predict the prognosis of patients with myocardial infarction. Conclusion The serum level of periostin may be related to the prognosis of cardiovascular disease in patients with AMI.