The influence of different femoral alignment systems on blood loss and the need for blood transfusion after total knee arthroplasty (TKA) was studied. The blood loss was retrospectively recorded in two similar groups of consecutive patients. The first group consisted of 46 patients in whom TKA was performed using the intramedullary femoral alignment system and the second group consisted of 45 patients in whom the procedure was performed with the extramedullary system. In the intramedullary group, the mean volume of drained blood was 758 mL, whereas in the extramedullary group it was 613 mL (P < .05). More patients in the intramedullary. group required blood transfusions, but no significant difference was noted in the number of blood units transfused per patient. Extramedullary femoral alignment instrumentation reduces blood loss after cementless TKA.