The purpose of this retrospective study was to assess whether tranexamic acid (TXA) reduces blood loss in cementless total knee arthroplasty (TKA) comparable to levels observed with cemented fixation. After exclusions from 109 consecutive TKAs, 76 cementless knees were matched to 78 cemented knees of identical implant and surgeon. Blood loss with and without TXA was compared. There was no difference between cohorts in sex, age, body mass index, American Society of Anesthesiologists Physical Status classification, or preoperative hemoglobin ( ≥ 0.119). Use of TXA reduced median drain output by only 205 mL in cementless knees compared to 470 mL in cemented knees ( < 0.001). Median drain output per hour was highest in cementless knees without TXA (39.5 mL) followed by cemented knees without TXA (38.2 mL), cementless knees with TXA (28.5 mL), and cemented knees with TXA (12.7 mL;  < 0.001). Hemoglobin drop and total blood loss did not differ between cohorts regardless of TXA use. Cementless fixation in TKA resulted in greater intra-articular blood loss as measured by drain output, despite the use of TXA. Further research is warranted to examine whether a higher TXA dose, TXA delivery method, or the application of bone wax sealant would mitigate blood loss in cementless TKA, and subsequently whether intra-articular blood accumulation resulting in postoperative hemarthrosis affects recovery, function, and clinical outcomes.