The present study is the premier clinical attempt to scrutinize the practicability of prophylactic fibrinogen infusion in patients undergoing heart transplantation (HT). A total of 67 consecutive patients who had undergone HT between January 2012 and December 2014 were assessed. After exclusion of some patients, 23 patients were given preoperative 2 g fibrinogen concentrate over a period of 15 minutes after the termination of cardiopulmonary bypass pump and complete reversal of heparin, and 30 patients were not given. Some laboratories were measured before general anesthesia and at 6 and 24 hours after surgery. In addition, major adverse events were also evaluated during hospitalization. The mean age of the patients was 39.5 ± 11.4 years, with a predominance of male sex (77.4%). All laboratories at baseline were comparable between groups. The length of hospital stay was longer in the control group compared to the fibrinogen group (20 [16-22] vs 16 [12-19] days; P = .005). There was a trend for patients in the fibrinogen group to have more acute kidney injury (AKI) after surgery (10% vs 30.4%) and less reoperation for bleeding (20% vs 8.7%). The amount of postoperative bleeding was significantly higher in the control group compared to the fibrinogen group (P < .001). The number of packed red blood cell transfused during 24 hours after surgery was significantly lower in the fibrinogen group (P < .001). The transfusion of fibrinogen in patients undergoing HT may be associated with reductions in postoperative bleeding, the number of packed red blood cells, and hospital length of stay; however, it may enhance postoperative AKI.