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For successful, fast-onset sciatic popliteal block (SPB), either a single injection above the division of the sciatic nerve, or 2 injections to block the tibial nerve (TN) and common peroneal nerve (CPN) separately have been recommended. In this study, we compared the traditional nerve stimulator (NS)-guided SPB above the division of the sciatic nerve with the ultrasound (US)-guided block with single injection of local anesthetic (LA) between the TN and CPN at the level of their division. We hypothesized that US-SPB with a single injection between TN and CPN would result in faster block onset than a single-injection NS-SPB.Fifty-two patients were randomized to receive either an NS-SPB or a US-SPB. For both blocks, a single injection of 20 mL mepivacaine 1.5% was given using an automated injection pump while controlling for injection force. For NS-SPB, a TN response below 0.5 mA was sought 7 cm above the popliteal fossa crease (and proximal to the divergence of the TN and peroneal nerves). For US-SPB, the injection was made after a US-guided needle was inserted between the TN and CPN at the level of their separation. Motor response was not actively sought but registered if present. The location and spread of LA were evaluated by US in both groups. Onset of motor and sensory blocks was serially assessed in 5-minute intervals in the TN and CPN divisions and compared between the groups.All patients in both groups had successful block at 30 minutes after the injection, defined as sensory block to allow surgery without supplementation. A higher proportion of patients in the US-SPB group had a complete sensory (80% vs 4%, P < 0.001) and motor block (60% vs 8%, P < 0.001), defined as anesthesia and paralysis in all nerve territories, at 15 minutes after injection. US signs of intraepineural injection were present in 19 patients (73%) in the NS-SPB group and 25 patients (100%) in the US-SPB group (P < 0.001).A single injection of LA in US-SPB with needle insertion at the separation of the TN and CPN results in a similar success rate at 30 minutes; however, more patients in the US-SPB group than in the NS-SPB group had complete block at 15 minutes.