Red blood cell concentrates (RCC) substitution after total knee arthroplasty (TKA) is correlated with multifold of complications and an independent predictor for higher postoperative mortality. TKA is mainly performed in elderly patients with pre-existing polymorbidity, often requiring permanent preoperative antithrombotic therapy (PAT). The aim of this retrospective analysis was to investigate the impact of demand for PAT on inpatient blood management in patients undergoing TKA. In this study 200 patients were retrospectively evaluated after TKA for differences between PAT and non-PAT regarding demographic parameters, preoperative ASA score > 2, duration of operation, pre-, and intraoperative hemoglobin level, and postoperative parameters including amount of wound drainage, RCC requirement, and inpatient time. In a multivariate logistic regression analysis the independent influences of PAT, demographic parameters, ASA score > 2, and duration of the operation on RCC demand following TKA were analyzed. Patients with PAT were significantly older, more often had an ASA > 2 at surgery, needed a higher number of RCCs units and more frequently and had lower perioperative hemoglobin levels. Multivariate logistic regression revealed PAT was an independent predictor for RCC requirement. PAT patients are more likely to require RCC following TKA and should be accurately monitored with respect to postoperative blood loss.