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Introduction: Performance of painful diagnostic and therapeutic procedures is common in emergency department (ED), and procedural sedation and analgesia (PSA) is a fundamental skill for every emergency physician. This studywas aim to compare the efficacy of remifentanil with fentanyl/midazolam in painless reduction of anterior shoulder dislocation. Methods: In this randomized, double blind, clinical trial the procedural characteristics, patients satisfaction as well as adverse events were compared between fentanyl/midazolamand remifentanil for PSA of 18–64 years old patients, which were presented to ED following anterior shoulder dislocation. Results: 96 cases were randomly allocated to two groups (86.5% male). There were no significant difference between groups regarding baseline characteristics. Remifentanil group had lower duration of procedure (2.5§1.6 versus 4.6§1.8 minutes, p Ç 0.001), higher pain reduction (53.7§13.3 versus 33.5§19.6, p Ç 0.001), lower failure rate (1 (2.1%) versus 15 (31.3%), p Ç 0.001), higher satisfaction (p Æ 0.005). Adverse events were seen in 12 (25%) patients in midazolam/fentanyl and 8 (16.7%) cases in remifentanil group (p Æ 0.122). Conclusion: It seems that use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedure as well as higher patient satisfaction in comparison with midazolam/fentanyl combination in anterior shoulder dislocation.