The purpose of this study was to compare the efficacy and safety of extended-release epidural morphine (EREM) and perineural infusion (PNI) to control pain after total knee arthroplasty. A convenience sample of 200 patients was obtained using a retrospective chart review of patients who underwent a total knee arthroplasty. Institutional review board approval was obtained, and 100 charts of patients who received EREM and 100 patient charts for PNI were reviewed. The main end points were pain scores up to 48 hours postoperatively, and the ancillary end points were supplemental opioid requirements and adverse effects. Data were analyzed using the Pearson chi2 where appropriate or the Fisher exact test, and all continuous variables were examined using a Wilcoxon rank test. The results of the study showed no significant differences between the 2 groups for the levels of pain preoperatively, immediately postoperatively, and at 48 hours postoperatively. However, at both 12 hours and 24 hours postoperatively, the PNI group had a significantly higher pain score than the EREM group. The EREM group had better pain scores; however, one must look at a number of different variables when deciding if EREM is the correct choice for postoperative pain management.