Introduction: Recovery from anesthesia induced with inhalation agents can be distressing because of prolonged mental function deficiency, disorientation and abnormal neurological reflexes. So we designed this study to compare the effect of flumazenil versus aminophylline on cognitive and neuromotor status after isoflurane anesthesia.Materials and methods: To conduct this randomized, placebo-controlled, double-blinded study, 90 ASAI-II patients who underwent orthopedic surgery under N2O/O2 plus isoflurane anesthesia were administered flumazenil 1mg, aminophylline 2mg/Kg or placebo upon emergence from anesthesia, and their vigilance and neurological recovery were assessed.Results: Comparison of three groups in vigilance score showed significant statistical difference at minute 5, 10, 20. (p<0.001, p=0.016). Recovery of vigilance in flumazenil treated patients compared to those who received aminophylline was faster at minutes of 5, 10 and 20 (p=0.001, p=0.001, p=0.038) and in aminophylline treated patients compared to placebo group was better at 5, 10, 20 and 30 minutes (p<0.001, p=0.1001, p=0.008 and p=0.04).Neurological score between there groups at 5, 10, 20, 30 minutes has signification statistical difference (p<0.001, p<0.001, p=0.001 and p=0.048). Neurological score showed better recovery of flumazenil treated patients compared to aminophylline treated patients at minutes 5 and 10 (p=0.001, p=0.005). Neurologic recovery in aminophyllne group was faster than placebo group at minute 5, 10 and 20 (p=0.028, p=0.001, and p=0.013).Conclusion: This study showed that bolk flumazenil and amynophyline are effective in improving recovery of vigilance and neuromotor functions following isoflurane anesthesia, but flumazenil proved to be more effective.