Background: Ultrasound guidance has become a standard method for detection of nerve structures in regional anesthesia. During ultrasound-guided blockade, to identify anatomical structures is crucial but can be challenging. In clinical practice, we find a wide difference in the visibility score of the sciatic nerve (SN) through different approaches. This study aimed to compare SNB through the anterior and above-knee lateral approach in terms of identification ease, performance efficacy, and safety.Methods: Patients scheduled for below-knee surgery were randomized to either receive SNB using the above-knee lateral approach (Group L, n=27) or the anterior approach (Group A, n=26). The primary outcome was the visibility score of SN. Secondary outcomes included the time taken to identify the SN, nerve depth, success rate of SN identification, number of needle passes, time to elicit foot flexion, needle depth, and occurrence of SNB complications. Additionally, the sensory block onset and analgesia duration were assessed.Results: We included 53 adult patients. Compared with Group A, Group L showed a higher SN visibility score [3.25 (3.17, 3.67) vs. 2.50 (1.86, 2.68), P<0.001]. The scan time was significantly shorter in Group L 8.70 (6.01) s vs. 31.54 (11.87) s, P<0.001). The depth of the SN was 3.20 (0.56) cm in Group L and 5.53 (0.84) cm in Group A (P<0.001), and the needle insertion depth was 7.15 (0.90) cm in group L and 8.32 (1.13) cm in Group A (P<0.001). The number of needle passes was less in Group L, as well as the time to elicit foot flexion, and the time taken to perform the SN block (all P<0.001). The success rate of SN identification was non-significantly higher in Group L. There was no significant between-group difference in the onset of sensory block, as well as postoperative analgesia duration. None of the approaches involved acute systemic toxicity and hematoma occurrence.Conclusions: Based on the visibility score, the above-knee lateral approach allowed easy SN identification and safe SNB. Using the ultrasound-guided above-knee lateral approach for SNB in below-knee surgeries could be a reliable choice.