OBJECTIVE Orthotopic liver transplantation (OLT) has been associated with high blood transfusion requirements. We evaluated the transfusion needs and frequency of alloimmunization to RBC antigens among OLT recipients pre- and post-transplantation. METHODS We reviewed the medical records of patients who underwent a first OLT between January 2007 and June 2017. Transfusions given only during the perioperative period, defined by 1 week before OLT until 2 weeks following OLT, were included in this study. Records were reviewed in June 2019 for updated antibody testing results. RESULTS A total of 970 patients underwent OLT during the study period. The median age of patients was 57 years; 608(62.7%) were male. During the perioperative period, transfused patients received an average of 10.7 (±10.7) RBC units, 15.6 (±16.2) thawed plasma units and 4.1 (±4.3) platelet units. At the time of OLT, a total of 101 clinically significant RBC alloantibodies were documented in 58(5.98%) patients. Fifty-three of these antibodies were directed against Rh blood group antigens. Twenty-two (37.9%) patients had more than one alloantibody. Patients with alloimmunization before OLT (N = 58) received perioperatively comparable number of RBCs to non-alloimmunized patients (10.5 ± 10.6 vs. 9.6 ± 10.7; p = 0.52). There was no significant difference in perioperative or intraoperative RBC transfusion between patients with one alloantibody and those with multiple alloantibodies. Only 16 patients (16/737; 2.17%) developed new alloantibodies at a median of 61 days after OLT. The overall alloimmunization rate was 9.8% (72/737), and female patients were more likely to be alloimmunized. CONCLUSIONS Blood transfusion requirements in OLT remain high. However, the rate of RBC alloimmunization was not higher than the general patient population.