The purpose of this clinical prospective, randomized, double-blind study was to compare the anesthetic efficacy of 4% articaine with epinephrine (1:100,000) and without epinephrine in inferior alveolar nerve block anesthesia for extractions of mandibular teeth. Eighty-eight patients received intraoral inferior alveolar nerve blocks using 4% articaine with 1:100,000 epinephrine (n = 41; group 1) or without epinephrine (n = 47; group 2) for extractions of mandibular teeth. The primary objectives were differences in onset as well as in length of soft tissue anesthesia. The amount of anesthetic solution, need of a second injection, pain while injecting, pain during treatment, postoperative pain, and possible complications were surveyed. In both groups, anesthesia was sufficient for dental extractions. In group 1, a significantly faster onset of the anesthetic effect (7.2 min vs. 9.2 min; P = .001) and a significantly longer duration of soft tissue anesthesia (3.8 h vs. 2.5 h; P < .0001) were seen. There was no significant difference in the amount of anesthetic solution needed, in the need for a second injection, in the injection pain, in pain during treatment, or in postoperative analgesia. In both groups, no complications were seen. To minimize the epinephrine-induced side effects, 4% articaine without epinephrine is a suitable anesthetic agent for dental extractions in the mandible after inferior alveolar nerve block anesthesia. There could be less postoperative discomfort due to the shorter duration of anesthesia without increased postoperative pain.