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Objectives This double blinded, placebo controlled randomized clinical trial studies the effect of exenatide on myocardial infarct size. The glucagon-like peptide-1 receptor agonist exenatide has possible cardioprotective properties during reperfusion after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods 191 patients were randomly assigned to intravenous exenatide or placebo initiated prior to percutaneous coronary intervention using 10 μg/h for 30 min followed by 0.84 μg/h for 72 h. Patients with a previous myocardial infarction, Trombolysis in Myocardial Infarction flow 2 or 3, multi-vessel disease, or diabetes were excluded. Magnetic resonance imaging (MRI) was performed to determine infarct size, area at risk (AAR) (using T2-weighted hyperintensity (T2W) and late enhancement endocardial surface area (ESA)). The primary endpoint was of 4-month final infarct size, corrected for the AAR measured in the acute phase using MRI. Results After exclusion, 91 patients (age 57.4 ± 10.1 years, 76% male) completed the protocol. There were no baseline differences between groups. No difference was found in infarct size corrected for the AAR in the exenatide group compared to the placebo group (37.1 ± 18.8 vs. 39.3 ± 20.1%, p = 0.662). There was also no difference in infarct size (18.8 ± 13.2 vs. 18.8 ± 11.3% of left ventricular mass, p = 0.965). No major adverse cardiac events occurred during the in-hospital phase. Conclusion Exenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]