Increasing demand for donor organs has led to new pharmacological concepts for reducing ischemia-reperfusion injury (I/R) of the graft after liver transplantation to prevent primary non-functioning of the organ. Prostaglandins have proved to be cytoprotective in several experimental models of ischemia and transplantation. The prophylactic administration after orthotopic liver transplantation is still a subject of controversial discussion. The aim of our study was the evaluation of the post-transplant hepatic artery resistive index (RI) measured by color Doppler imaging, in combination with postoperative elevation of transaminases, as parameters indicating the need for a differentiated systemic therapy with prostaglandin E1 (PGE1) (alprostadil). In addition, the value of serum procalcitonin (PCT) as a postoperative parameter for the extent of I/R is investigated. In the case of post-transplant elevated hepatic artery RI (RI > 0.75), the administration of PGE1 led to a significant reduction of transaminases (p < 0.05) and a decline of the RI. In addition, postoperative PCT levels could be reduced significantly by PGE1 application. These results suggest that determination of RI is feasible for indicating a need for therapy with PGE1. Its targeted application reduces hepatocellular damage due to I/R after liver transplantation.