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The lateral and anterior approaches for proximal sciatic nerve (SN) block can be used in patients lying supine. We assume that the posterior femoral cutaneous nerve (PFCN) is simultaneously blocked more often via the lateral approach than via the anterior approach, given the proximity of these 2 nerves at the injection level. However, locating the SN is difficult when using the original landmark-based lateral approach. We have introduced ultrasound guidance to alleviate the technical difficulty of the lateral approach and tested the hypothesis that an ultrasound-guided lateral approach would achieve PFCN block more often than the ultrasound-guided anterior approach for SN block.Forty consecutive patients undergoing knee surgery were randomly allocated to receive an SN block using an ultrasound-guided lateral or anterior approach. The primary outcome was the frequency of PFCN block 30 minutes after SN block. Secondary outcomes included the frequency of SN block, nerve depth, needle depth, and time taken to perform the block. We also assessed the spread of injectate by the lateral approach in 4 cadaveric legs.The frequency of PFCN block 30 minutes after SN block was higher with the lateral approach than with the anterior approach (60% vs 15%, P = 0.008). The frequency of SN block was comparable between the groups. Dye reached the PFCN in all cadaveric specimens.The ultrasound-guided lateral approach for proximal SN block can be performed as successfully as the anterior approach and provides PFCN block more often than the anterior approach.Clinical Trial Registration: This study was registered at UMIN Clinical Trials Registry, identifier UMIN000026748.