While adenosine and dipyridamole as myocardial perfusion imaging (MPI) stress agents have literature supporting their safety in the setting of myocardial infarction (MI), regadenoson does not. Studying a high risk cohort of patients with elevated cardiac biomarkers may shed light on potential safety issues of these agents which might also affect lower risk cohorts. All patients who had undergone a clinically indicated stress MPI study at two academic centers from 1/1/2010 through 12/31/2012 with elevated troponin a7 days prior to testing were included. The primary endpoint was a composite of death, non-fatal MI, congestive heart failure (CHF), stroke, ventricular arrhythmias, atrial fibrillation/flutter, or atrioventricular block requiring intervention within 24 h of testing. Of the 703 stress MPI studies that met inclusion criteria, 360 (51.2%), 199 (28.3%), 74 (10.5%), 9 (1.3%), and 61 (8.7%) underwent regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively. The primary endpoint occurred in 11 (1.6%) patients with an incidence of 1.4% (n = 5), 1.0% (n = 2), 1.4% (n = 1), 11.1% (n = 1), and 3.3% (n = 2) following regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively (P = 0.137). The adverse events included non-fatal MI in 7 (1.0%) patients, death in 1 (0.1%) patient, CHF in 1 (0.1%) patient, ventricular arrhythmia in 1 (0.1%) patient, and atrial arrhythmia in 1 (0.1%) patient. In the setting of elevated troponin, serious complications associated with either exercise or vasodilator stress testing appear to be relatively rare with no increased risk attributable to a particular vasodilator agent.