Background and Objectives:  Total-knee replacement (TKR) surgery is one of the most painful orthopedic procedures after surgery. Opioid has been commonly combined with a local anesthetic to improve the quality of pain relief, but the treatment has opioid-related side effects.  This study compared the cost effectiveness of patient-controlled epidural analgesia (PCEA) with 0.0625% bupivacaine plus fentanyl (BF) 3 µg/ml versus 0.15% ropivacaine alone (R) during the first 48 hours after TKR procedure.  Methods: This prospective randomized double-blinded study was performed on 70 patients who underwent unilateral TKR procedure and received either BF or R after surgery. Visual analog scale (VAS) pain score at rest and upon movement, side effects, and cost of treatment were compared.  Results: Overall pain at rest and upon movement between groups was not significantly different (p=0.58, 95% CI = 4.4 to -7.8 and p= 0.8, 95% CI = 6.4 to -8.2, respectively). Patients in the BF group experienced more pruritus and had more vomiting episodes than those in the R group (p = .015), whereas no difference group compared with that in the R group. In addition, pain treatment with bupivacaine and fentanyl was 18% less costly compared with ropivacaine alone. Conclusions: Considering the economic evaluation, we conclude that PCEA with .0625% bupivacaine plus fentanyl 3µg/ml is more cost effective and provides more patient satisfaction than PCEA with ropivacaine alone. However, use of epidural ropivacaine alone causes fewer opioid-related side effects, particularly pruritus and vomiting,