We report about detailed hemodynamic changes and one major cardiac complication occurring after submucosal injection of epinephrine (1 : 10 000) for management of upper gastrointestinal bleeding in a series of four consecutive patients. Cardiac contractility and afterload, determined by the cardiac index and the systemic vascular resistence index (SVRI), were assessed by transpulmonary thermodilution using the Pulse Contour Cardiac Output monitoring system (PiCCO; Pulsion Medical Systems, Munich, Germany), and the mean arterial pressure and heart rate were recorded. We observed a distinct rise in both mean arterial pressure and heart rate, and this effect was pronounced in the three patients with esophageal lesions. The increase in the mean arterial pressure was caused by an elevation of the cardiac index in two patients, a rise in both cardiac index and SVRI in one patient, and a rise in the SVRI only in the fourth patient. One patient, who had received 30 ml epinephrine for treatment of a bleeding Mallory-Weiss tear, developed an acute myocardial infarction during the postprocedural follow-up period. In conclusion, submucosal injection of epinephrine may cause significant hemodynamic changes that can potentially lead to adverse cardiac events. Close cardiac monitoring during and after submucosal application of epinephrine therefore seems a prudent precaution. In the treatment of esophageal lesions, the total amount of epinephrine injected should be carefully titrated, so that the lowest possible volume that achieves adequate hemostasis is used.