Objective: The aim of this study was to compare preemptive analgesia of oral ketorolac plus submucous local placebo with oral ketorolac plus submucous local tramadol after impacted mandibular third molar surgery. Study design: A double-blind, randomized, placebo-controlled clinical trial was conducted. Patients were randomized into two treatment groups (n = 15 per group): group A, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local placebo (1 mL saline solution); group B, oral ketorolac 10 mg, 30 minutes before surgery plus submucous local tramadol (50 mg diluted in 1 mL saline solution). We evaluated the intensity of pain, time for the first analgesic rescue medication, and total analgesic consumption. Results: Pain intensity, number of patients requiring analgesic rescue medication, number of patients in each group not requiring analgesic rescue medication, and total analgesic consumption showed statistical significance. Conclusions: Preemptive use of oral ketorolac plus submucous local tramadol is an alternative treatment for acute pain after surgical removal of an impacted mandibular third molar. © Medicina Oral S. L.