BACKGROUND: Intra-articular (IA) bupivacaine, morphine, or neostigmine were known to produce an analgesic effect in knee arthroscopic surgery. But there were some arguing reports about the analgesic efficacy of addition of morphine or neostigmine into IA bupivacaine and IA administration of these drugs in a simple arthroscopic surgery. We performed this study to determine whether the addition of morphine or neostigmine into IA bupivacaine produces superior analgesic effect or increases patient satisfaction than IA bupivacaine alone. METHODS: Fifty-one patents for simple arthroscopic knee surgery were allocated to 4 groups following their addition into IA 0.5% bupivacaine 20 ml; placebo (Group 1, n = 10), neostigmine 500ng (Group 2, n = 16), morphine 2 mg (Group 3, n = 11) or neostigmine 250ng and morphine 1 mg (Group 4, n = 14). Anesthesia was performed with propofol, fentanyl and vecuronium. The VAS scores and patient satisfaction in 1, 3, 6, 12, and 36 hours after surgery were compared in addition to the side effects between groups. RESULTS: The VAS score of Group 2 (2.6 +/- 0.8), 3 (2.8 +/- 0.4) and 4 (2.3 +/- 0.9) are lower than that of Group 1 (3.3 +/- 0.7) at 1 hour after surgery (P = 0.038). The VAS scores were decreased by the following order: Group 1, Group 2 or 3 and Group 4, at 1 and 24 hours after surgery, (P = 0.048 and 0.036 respectively). The distribution of patient satisfaction was significantly different at 24 hour after surgery (P = 0.036), in which rate of patients showing good or fair in Group 2, 3 and 4 were larger than that of Group 1 (P = 0.057, 0.032 and 0.014, respectively). There was no significant difference in the incidence of side effects between groups. CONCLUSIONS: We concluded that the addition of morphine 2 mg, neostigmine 500ng or each morphine 1 mg and neostigmine 250ng into IA bupivacaine showed a similar analgesic effect, patients satisfaction and side effect during 36-hours postoperative period, compared with IA bupivacaine alone, except for the better analgesic effect in an immediate-postoperative period.