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Background: This double-blinded, randomized clinical trial was designed to evaluate the comparison of intravenous versus intraarticular (IA) administration of midazolam on postoperative pain after knee arthroscopy. Materials and Methods: In this study, 75 patients randomized in three groups to receive 75 mc/kg IA injection of midazolam and 10 ml intravenous injection of isotonic saline (Group I), 75 mc/kg intravenous injection of midazolam and 10 cc IA injection of isotonic saline (Group II) or IA and intravenous injection of isotonic saline (Group III) at the end of knee arthroscopy. Pain scores, time until the first request for analgesics, cumulative analgesic consumption, satisfaction, sedation, and complications as studied outcomes were assessed. Patients were observed for 24-h. Results: IA administration of midazolam significantly reduced pain scores in the early postoperative period compared with intravenous injection. Mean of time to first analgesic requirement in Group III (33.6 min) was significantly lower than Group II (288.8 min) and Group I (427.5 min). Cumulative analgesic consumption was increased in Groups II (35.5 mg), and III (70 mg) compared with Group I (16 mg), (P < 0.0001). Complications significantly occurred in 3 of 25 patients in Group I in contrast to 20 of 25 patients in Group III (P < 0.0001). At 2-, 4- and 8-h after arthroscopy pain score significantly decreased in Group I than other groups (P < 0.0001). Patients in Group I were significantly satisfy than other groups (P < 0.0001). Conclusion: Results show the greater analgesic effect after IA administration of midazolam than after intravenous injection and hence, IA administration may be is the method of choice for pain relief after knee arthroscopy.