Achieving successful anesthesia and pain control in a predictable, efficient manner is a challenge in the endodontic treatment of vital inflamed lower molars. The aim of this study was to evaluate the effect of oral ketamine on the dosage of local anesthetics required and postoperative pain management for irreversibly inflamed mandibular molars. In this randomized double-blind placebocontrolled clinical trial, 36 patients with irreversibly inflamed mandibular molars were randomly divided into two groups of 18. Ten mg of ketamine dissolved in 20 ml of fruit juice was administered orally to patients in the experimental group. The control group was given 20 ml of fruit juice alone as a placebo. After 30 min, inferior alveolar nerve block (IANB) anesthesia was induced using one cartridge of 2% lidocaine and 1:100000 epinephrine. Teeth were tested after 5 to 10 min using an electrical pulp tester. In patients showing a positive response, another IANB injection was applied, and the total number of anesthetic cartridges used was recorded. Postoperative pain was evaluated using a visual analogue scale (VAS). In addition, use of analgesic in the first 24 h after treatment was monitored using a questionnaire. Data were analyzed by t test using SPSS software. There were no significant differences in age or gender between the two groups. The number of anesthetic cartridges used in the ketamine group was significantly less than that in the control group (P = 0.003). Furthermore, postoperative pain in the ketamine group was significantly lower (P = 0.019). Also the number of analgesic tablets taken in the ketamine group was significantly lower (P = 0.011). It can be concluded that a low dose of ketamine might be beneficial for enhancing the effect of local anesthetics. (J Oral Sci 53, 461-465, 2011)