In this randomized, double-blind, sham-controlled study the investigators evaluated the efficacy and safety of phentolamine mesylate (PM) in shortening soft-tissue anesthesia after intraoral 3% mepivacaine without vasoconstrictor inferior alveolar mandibular block. A total of 44 subjects received one or two cartridges of 3% mepivacaine plain local anesthetic using a standard injection technique to achieve profound lower lip anesthesia, followed 30 minutes later, in the same location and in a blind fashion, by either PM or sham injection (in which the needle does not penetrate the tissues) using the same technique and in a 1:1 cartridge ratio. The subjects were observed for four hours during which duration of soft tissue anesthesia and oral function were evaluated, oral exams were performed and vital signs were recorded. The median time to recovery of normal sensation of the lower lip after PM/sham injection was 160 minutes (±13 min) in the sham group and 95 minutes (± 12 min) in the PM group, for a reduction in duration of numbness of 65 minutes (41%) in the PM group as compared to the sham treatment group. We did not observe a statistically significant reduction in recovery time for the tongue, nor a hastened return to normal oral function as compared to the subjects who received sham injections. Additionally, PM appeared to be well tolerated, with no clinical adverse effects.