Background Periarticular local infiltration of analgesia (LIA) and regional nerve block using adductor canal block (ACB) have been described as effective in managing postoperative pain for total knee arthroplasty (TKA). It has been shown that combining ACB with LIA can significantly reduce pain scores and postoperative consumption of morphine compared with LIA alone. However, this may raise concerns about the potential risk of local anesthetic systemic toxicity (LAST), especially with the large doses of total local anesthetic used in both LIA and ACB. The purpose of this study was to evaluate the plasma level of bupivacaine over a 72-hour period following ACB using 66.5 mg of liposomal bupivacaine (LB) in patients undergoing TKA with LIA using 300 mg ropivacaine. This study aims to provide some pharmacokinetic (PK) data of LB in ACB for future dose defining study on LB in ACB together with LIA. Methods This was a prospective observational study. Ethical approval for this study (Reference Number UW 20 -589) was provided by the Ethical Committee, Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster, Queen Mary Hospital, Hong Kong (Chairman Prof. Brian Lang) on 6 October 2020. Ten patients undergoing primary, unilateral, simple revision TKA were included in the study from December 2020 – February 2022. The primary outcomes were the time to peak plasma concentration (Tmax) of bupivacaine and the peak plasma concentration (Cmax) of bupivacaine. The secondary outcome was the presence of LAST. Results Tmaxof bupivacaine was 48 hours while Cmax of bupivacaine was 88 mcg/L, this value was far below 2000 mcg/L, the defined toxic plasma concentration of bupivacaine. Conclusions The report's only validity resides with the dataset describing Tmax and Cmax of LB in a small cohort undergoing TKR. Trial registration The clinical trial was registered at ClinicalTrials.gov on 07/06/2021 with registration number NCT04916392.