OBJECTIVES: To assess the effect of persistence on statin, a-blocker, or Calcium Channel Blocker (CCB) therapy, on the risk of reinfarction in a Medicaid high-risk, largely female, predominantly minority population. METHODS: Prospective nonconcurrent cohort, longitudinal data analysis of medical and pharmacy claims of Acute Myocardial Infarction (AMI) Medicaid MCO patients, observed between January 1, 2002 and December 31, 2004. Cox proportional hazards models were used to predict the likelihood of a reinfarction as a function of persistence on the first medication post-AMI, adjusting for age, race, sex, heart disease and other comorbidities, and other medications. RESULTS: Among 515 AMI patients (58% female and 54% African American), hypertension (91%) and heart disease (81%) were the most prevalent comorbidities; most initial AMIs were non-transmural. Discontinuation of statin, a-blocker, or CCB post-AMI increased the likelihood of a reinfarction (HR=1.66; 95%CI 1.03-2.69). Concurrent heart disease, hyperlipidemia, or renal disease significantly increased the likelihood of a reinfarction. Age, race and sex did not significantly predict the likelihood of reinfarction. CONCLUSION: Persistence on the first post-AMI preventive medication is effective at avoiding a reinfarction. Concomitant heart disease, renal disease and hyperlipidemia increases the likelihood of a reinfarction.