Treatment with the endothelial modulator prostacyclin may be beneficial in patients with endothelial dysfunction. The primary aim of the present pilot study was to evaluate the safety and the potential endothelial modulating affect of the prostacyclin analog iloprost in patients with a recent ST segment elevation myocardial infarction (STEMI). Seventeen patients were randomized to either 24h of iloprost infusion in combination with low dose eptifibatide infusion or saline infusion+eptifibatide. The study was randomized and open labeled. None of the patients experienced any bleeding complications and vital signs were stable throughout the entire study period in both groups. None of the functional hemostatic whole blood assays applied in the present study differed between the active treatment and the placebo group. The endothelial marker, sE-selectin, displayed a decrease over time in the iloprost group but increased in the placebo group (p=0.008), whereas none of the other biomarkers of endothelial cell and glycocalyx activation or damage differed significantly between the groups. In this pilot study, infusion of a prostacyclin analog appeared safe and has a detectable modulating effect of activated endothelium in patients with a recent STEMI. ClinicalTrials.gov: NCT01179776.