Background and Objectives. The acetylcholinesterase inhibitor neostigmine has shown peripherally mediated analgesic action in recent preclinical and clinical studies. The present study investigates the effectiveness of adding neostigmine to a local anesthetic, mepivacaine, in patients receiving axillary brachial plexus block for upper extremity surgery. Methods. In a double-blind, randomized study 34 patients were assigned to the treatment group: Neostigmine (NM) (500 mu g) + mepivacaine (M) (500 mg) (NM, n = 17) as drugs for the plexus block, or to control group: mepivacaine (500 mg) + saline (0.9%, 1 mt) (M, n = 17). Results. The onset and duration of sensory and motor block was similar in both groups. Patients receiving NM had significantly lower pain ratings [visual analogue scores (VAS): 14.7 +/- 9.9 vs 32.4 +/- 23.5; P <.05] 24 hours after surgery, and a lower number of patients in the NM group needed supplemental analgesics during the first 24 hours postoperatively. No adverse events were recorded for either group. Conclusions. Peripherally administered neostigmine improves postoperative analgesia in axillary brachial plexus block.