OBJECTIVES: The FDA requires antihyperglycemic agents to demonstrate CV safety at the time of and after marketing approval.  Since CV safety trials have specific entry criteria in patients with T2DM, the generalizability of results to the broader T2DM population remains questionable.  This real-world retrospective analysis estimated the proportion of patients with T2DM who met inclusion and exclusion criteria from the EMPA-REG Outcomes trial. METHODS: Adult patients with the first T2DM diagnosis (ICD-9-CM 250.x[0,2]) claim (index date) from 01/01/2013 to 12/31/2014 or 06/30/2014 were identified from the Optum^TM Clinformatics^TM commercial and Truven MarketScan® (commercial and Medicare) databases, respectively.  In the primary analysis, a minimum of one-year look back was required to determine the proportion of patients who had a claim with an ICD-9 code for the following CV diseases: myocardial infarction, coronary artery disease, peripheral artery disease, unstable angina, and stroke.  Sensitivity analyses were performed in patients with minimum two or five-year of eligibility prior to index date.   RESULTS: The analyses included 299443, 817846, and 457325 patients from Optum, Truven commercial, and Medicare with mean age of 56, 54, and 75 years, respectively (samples were 262169, 742777, 405579, and 149140, 406791, 215540 for two-year and five-year cohorts). In the Optum database, the proportions with prior claims coded with the cardiovascular diseases of interest in the respective cohorts of one, two, or five-year minimum look back were 14, 15, and 18%; these proportions were similar in the Truven commercial population (11, 11, and 13%). Proportions for Truven Medicare were 28, 29, and 32%. CONCLUSIONS: In this analysis, the proportion of patients with T2DM meeting EMPA-REG Outcomes entry criteria was less than 20% for commercially-insured patients and approximately 30% for Medicare patients.  Although clinically important for patients with T2DM, the generalizability is limited and future CV-related research is needed.