The purpose of this study was to compare the analgesic and hemostatic effects of Local Infiltration Analgesia (LIA) with single injection femoral nerve block (SFNB). A database of patients undergoing knee arthroplasty between 2008 and 2013 was analyzed. A group of patients who underwent minimally invasive TKA either with SFNB (n = 112) or with LIA (n = 112) were matched. In the early postoperative period, the LIA group had a significantly lower VAS score, a lower drop in Hb and a lower length of hospital stay. Both the SFNB and LIA techniques provide excellent pain relief following TKA. Nevertheless, LIA reduces pain better in the very early postoperative period by a more complete nerve blockade allowing immediate postoperative mobilization and ambulation leading to a shorter hospital stay. Furthermore, LIA decreases perioperative blood loss by its local hemostatic effect.