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Although the anterior approach to the sciatic nerve block has rarely been performed due to lack of reliable surface anatomical landmarks and technical difficulty, ultrasound guidance may make performance of this approach easier. In this study, we evaluated the clinical use of the ultrasound-guided anterior approach to sciatic nerve block and compared this approach with the posterior approach in adults.One hundred patients undergoing minor knee surgery were randomly divided into two groups to receive anterior and posterior (subgluteal) approaches to sciatic nerve block, using 1.5% mepivacaine 20 mL with epinephrine combined with femoral and lateral femoral cutaneous nerve blocks. Both approaches to sciatic nerve block were performed using a low-frequency, 5 to 2 MHz, curved array transducer. Measurements included block execution time, depth and size of the nerve, needle depth, onset time of sensory and motor blockade, and duration of the block.The sciatic nerve was located significantly deeper and the needle depth was significantly greater in patients undergoing the anterior approach compared with the subgluteal approach. Both approaches were similar for execution time of sciatic nerve block, but the former took less time than the latter to perform all combinations of blocks. Although sensory block in the posterior femoral cutaneous nerve was achieved less often with the anterior approach compared with subgluteal approach (14.9% and 68.1%, respectively; P < 0.001), there were no differences in success rate, onset time or duration of blockade of the peroneal and tibial nerves between the two groups.The anterior approach to sciatic nerve block is performed as easily and successfully as the posterior approach using ultrasound guidance.