OBJECTIVE Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. METHODS Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anesthetic in the liquid was analyzed by liquid chromatography. RESULTS The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS Local anesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anesthetic blocks.