Background & Aim: One of the methods of controlling pain after knee arthroscopy is intra articular injection of morphine with or without local anesthesia. Pethidine is an opioid that also has week local anesthetic effect. The aim of this study was to compare the analgesic effect of intra-articular pethidine, bupivacaine and their combination at the end of knee arthroscopy on postoperative pain. Patients and Methods: After ethical approval, sixty patients(ASA I or II) undergoing arthroscopic knee surgery during general anesthesia were allocated to this double blinded clinical trial study. Premedication(midazolam and alfentanil) induction(propofol and atracurium) and maintenance(infusion of propofol and alfentanil by infusion pump, O2 and No2 50%, and bolus doses of atracurium) were similar in all groups. At the end of surgery, patients were randomly assigned to one of the three groups(20 patients in each group) to receive intra-articular 0.5% bupivacaine 100mg(Group B), pethidine 100 mg(Group M), or a combination of 0.5% bupivacaine 100 mg and pethidine 100 mg(Group BM) to a total volume of 20 ml. Methylprednisolone 40 mg was added to the solution of all the groups. After transfer to ward, Patient-Controlled Iv Analgesia(PCA) was given for pain control. Duration of postoperative analgesia, pain score(VAS) at 2, 6 and 12 hrs, first analgesic request, total fentanyl consumption during the first 24 hours and side effects were recorded. For statistical analyses, One way Anova, Tukey, Kruskal wallis, Mann-whitney(for quantitative variables) and Chi square or Fischer's Tests(for qualitative variables) were used. Results: Duration of postoperative analgesia was more prolonged in BM group than the other two groups, but M group did not show significant difference as compared to B group(211±51, 72±40, and 51±34 min, respectively). Time for first analgesic request was more prolonged in BM group than other two groups, and also longer in M group than B group(300±38, 132±60, and 82±45 min, respectively, P<0.05). Furthermore, total fentanyl consumption was significantly lower in BM group than other two groups, and also lower in M group than B group(307±52, 352±98, and 382±105mcg, respectively, P<0.05). Although, mean VAS was low in all groups and did not significantly differ between groups at 6 and 12 hrs, but at 2 hrs after surgery it was lower in BM group than others(P<0.05). Patient's satisfaction in BM group showed significant difference than the other two groups(P<0.05). No specific side-effects were observed. Conclusion: Intra-articular pethidine is a potential alternative to bupivacaine in knee arthroscopy. Furthermore, combination of pethidine and bupivacaine provided more therapeutic effects as compared to each used singly.