INTRODUCTION: Many patients experience pain with orthodontics, but there is no widely accepted standard of care for controlling orthodontic pain. Previous studies were inconclusive as to the most effective way to manage orthodontic pain. The purpose of this study was to assess the effectiveness in reducing pain of preemptive ibuprofen added to an ibuprofen regimen administered after separator placement. We also examined the contributions of psychological factors and sex to the experience of pain. METHODS: The subjects were randomly assigned to group A, 400 mg of ibuprofen 1 hour before separator placement (D1), 3 hours after placement (D2), and 7 hours after placement (D3); group B, placebo at D1, 400 mg of ibuprofen at D2 and D3; or group C, placebo at D1, D2, and D3. Before separator placement, the subjects completed 2 psychological surveys, a masticatory efficiency test, and a visual analog scale for expected pain and experienced pain during the masticatory efficiency test. After placement, the subjects recorded their actual pain, kept a pain diary for 24 hours after separator placement, and performed a 24-hour follow-up masticatory efficiency test. RESULTS: Group A, receiving ibuprofen before and after separator placement, experienced significantly less pain (P <0.05) at 6 hours, at bedtime, and at awakening on the second day. No contributions to pain were found for psychological factors or sex. CONCLUSIONS: Preemptive administration of analgesics should be recommended to orthodontic patients before separator placement.