A total of 54 patients (ages, 18-25) participated in this study at the Ahvaz Jundishapur University of Medical Science of Dentistry's Department of Orthodontics, undergoing separator placement were enrolled in this double blind cross over trial study. Subjects randomly assigned to 1 of 2 experimental groups: A; stage 1: 400 mg starch capsule, stage 2: 650 mg acetaminophen and stage 3: 400 mg ibuprofen, B; stage 1: 400 mg starch capsule, stage 2: 400 mg ibuprofen, stage 3: 650 mg acetaminophen. All medication taken orally half hour before separator placement. Also all medications were alike in appearance and were blind to each subjects and clinician. By the end of the 3 months, each subject had received 3 treatment. Each patient's level of discomfort was assessed with a 10-cm visual analogue scale (VAS), before of placement, immediately after placement, at 2, 12 hours and at morning time of 2, 3, 4 and 5 days. The pain evaluations were made during: chewing, biting and at rest. Patients were asked to complete a questionnaire at appropriate intervals during the week after separator placement. Subjects returned to clinic after 1 week for separator removal. Inclusion criteria: 1) no debilitating systemic disease; 2) currently not using analgesics; 3) no periodontal and endodontic problems in the right down quadrants. Exclusion criteria: haven't any conditions from inclusion criteria.