High volume infiltration with local anaesthetics (LIA) during total knee arthroplasty (TKA) for postoperative pain relief may be beneficial as compared to traditional methods. Retransfusion drains are used in TKA as alternative for allogeneic blood transfusions. When combining both modalities, recollected blood may contain large doses of local anaesthetics potentially leading to systemic toxicity during retransfusion. We investigated the safety of combining LIA and retransfusion of shed blood. Twenty patients scheduled for primary TKA were included. During surgery two peri-articular injections with ropivacaine (total 375 mg) were given. Patients received an intraarticular retransfusion drain and a wound catheter for continuous infusion of ropivacaine (8 mg/hr) for 24 hours. Blood collected in the retransfusion device, was not retransfused but used for laboratory analyses. Patients’ blood samples were taken immediately after surgery, 3, 6 and 24 hours postoperatively. We predicted cumulative ropivacaine concentrations using patient and shed blood samples from 6 hours postoperatively. We modelled instant retransfusion by estimating the cumulative plasma concentrations. Our safety threshold was 0.15 mg/L unbound ropivacaine in a venous plasma sample, based on literature. Total ropivacaine concentration was highest 24 hours postoperatively and unbound ropivacaine was maximal predominantly at 6 hours. Total ropivacaine concentrations ranged from 0.7 to 1.9 mg/L and unbound ropivacaine concentrations varied between 0.03 and 0.11 mg/L. At 6 hours median shed blood volume was 600 mL (range 303–869 mL). Interestingly was the difference (mean ± SD) in free fraction ropivacaine, in shed blood (68.8–4.6%) and in plasma (4.8 ± 1.1%). Assuming retransfusion, an average 13 mg (range 6–18mg) of unbound ropivacaine would have been administered intravenously. The model used to estimate cumulative ropivacaine plasma levels showed that instant retransfusion potentially would have led to unbound venous plasma concentrations of above 0.15 mg/L. Under the conditions in our study it is safe to use LIA in combination with continuous infusion of ropivacaine. However, in combination with the retransfusion of shed blood collected with the Bellovac ABT system this may lead to toxic levels. Before implementing the combination of both modalities formal testing is required.