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Patients undergoing total knee arthroplasty (TKA) have expected blood loss during and after surgery. The morbidity associated with blood loss and the burden of blood transfusions in adult arthroplasty necessitates preoperative optimization as routine practice. Current literature remains inconclusive on which TKA surgical instrumentation techniques are effective in minimizing perioperative blood loss, and consequently lower transfusion rates. The primary objective of this retrospective review, of a prospective randomized cohort study, was to compare surgical and patient factors, and their influence on blood loss and transfusions rates, between one type of patient-specific instrumentation (PSI), navigated computer-assisted surgery (CAS), and conventional TKA surgical techniques.A cohort of 128 matched patients (38 PSI, 44 CAS, 46 conventional surgeries) were compared. Preoperative factors analyzed included; age, gender, body mass index, preoperative hemoglobin (Hb) (g/L), international normalized ratio, use of anticoagulants and comorbid bleeding diathesis. Maximal Hb drop and transfusion requirements were compared on day 1 to 3. Perioperative factors collected included: surgical time, tourniquet time, drain output, in situ drain time, order of tibia or femoral cut, and intraoperative loss from suction.The three groups did not differ on the preoperative patient demographics examined. The difference between preoperative Hb and the lowest postoperative Hb readings did not differ between study groups (p = 0.39).There are no statistically significant differences in blood loss when comparing PSI versus CAS versus conventional TKA. Although emerging evidence on PSI is encouraging, the PSI technique for TKA does not result in reduced blood loss. The study was registered with ClinicalTrials.gov: NCT01145157.