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Background: Nerve stimulation and ultrasound guidance are the most popular techniques for peripheral nerve blocks. However, the minimum effective anesthetic volume (MEAV) in selected nerves for both techniques and the consequences of decreasing the local anesthetic volume on the pharmacodynamic characteristics of nerve block remain unstudied. We designed a randomized, double-blind controlled comparison between neurostimulation and ultrasound guidance to estimate the MEAV of 1.5% mepivacaine and pharmacodynamics in median and ulnar nerve blocks., Methods: Patients scheduled for carpal tunnel release were randomized to ultrasound guidance (UG) or neurostimulation (NS) groups. A step-up/step-down study model (Dixon method) was used to determine the MEAV with nonprobability sequential dosing based on the outcome of the previous patient. The starting dose of 1.5% mepivacaine was 13 and 11 mL for median and ulnar nerves at the humeral canal. Block success/failure resulted in a decrease/increase of 2 mL. A blinded physician assessed sensory blockade at 2-minute intervals for 20 minutes. Block onset time and duration were noted., Results: The MEAV50 (SD) of the median nerve was lower in the UG group 2 (0.1) mL (95% confidence interval [CI] = [1, 96] to [2, 04]) than in the NS group 4 (3.8) mL (95% CI = [2, 4] to [5, 6]) (P = 0.017). There was no difference for the ulnar nerve between UG group 2 (0.1) mL (95% CI = [1, 96] to [2, 04]) and NS group 2.4 (0.6) mL (95% CI = [2, 1] to [2, 7]). The duration of sensory blockade was significantly correlated to local anesthetic volume, but onset time was not modified., Conclusion: Ultrasound guidance selectively provided a 50% reduction in the MEAV of mepivacaine 1.5% for median nerve sensory blockade in comparison with neurostimulation. Decreasing the local anesthetic volume can decrease sensory block duration but not onset time.