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Background: Stress echocardiography (SE) is dependent on subjective interpretations. As a prelude to the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial, potential sites were required to submit two SE, one with moderate or severe left ventricular (LV) myocardial ischemia and one with mild ischemia. We evaluated the concordance of site and core lab interpretations.Methods: Eighty-one SE were submitted from 41 international sites. Ischemia was classified by the number of new or worsening segmental LV wall motion abnormalities (WMA): none, mild (1 or 2) or moderate or severe (3 or more) by the sites and the core lab.Results: Core lab classified 6 SE as no ischemia, 35 mild and 40 moderate or greater. There was agreement between the site and core in 66 of 81 total cases (81%, weighted kappa coefficient [K] =0.635). Agreement was similar for SE type - 24 of 30 exercise (80%, K = 0.571) vs. 41 of 49 pharmacologic (84%, K = 0.685). The agreement between poor or fair image quality (27 of 36 cases, 75%, K = 0.492) was not as good as for the good or excellent image quality cases (39 of 45 cases, 87%, K = 0.755). Differences in concordance were noted for degree of ischemia with the majority of discordant interpretations (87%) occurring in patients with no or mild LV myocardial ischemia.Conclusions: While site SE interpretations are largely concordant with core lab interpretations, this appears dependent on image quality and the extent of WMA. Thus core lab interpretations remain important in clinical trials where consistency of interpretation across a range of cases is critical.Trial Registration: ClinicalTrials.gov NCT01471522. [ABSTRACT FROM AUTHOR]