BACKGROUND: In this prospective, randomized, observer-blinded study, we compared double-injection (DI) ultrasound-guided supraclavicular block to a novel targeted intracluster-injection (TII) technique, whereby local anesthetic is injected inside the main and satellite neural clusters (confluences of trunks and divisions of the brachial plexus). METHODS: Ninety patients were randomly allocated to receive a DI (n = 45) or TII (n = 45) technique for ultrasound-guided supraclavicular block. The local anesthetic drug (lidocaine 1.5% with epinephrine 5 µg/mL) and total volume (32 mL) were identical in all subjects. In both groups, half the volume (16 mL) was injected inside the main neural cluster. For the DI technique, the second half (16 mL) was deposited at the "corner pocket" (intersection of the first rib and subclavian artery). In contrast, for the TII technique, the remaining half was divided into equal aliquots and injected inside every single satellite cluster. The main outcome variable was the total anesthesia-related time (sum of performance and onset times). RESULTS: Due to a quicker onset (mean ± standard deviation (SD): 10.1 ± 6.4 vs 18.5 ± 8.3 minutes; P < 0.0001), the total anesthesia-related time was shorter with the TII technique (21.2 ± 7.7 vs 27.7 ± 9.0 minutes; P = 0.001; 95% confidence interval for the difference of the means: 2.90-10.08 minutes). There were 0 (of 45) and 3 (of 45) surgical failures for the TII and DI group, respectively. Thus, the 2 methods achieved comparable rates of surgical anesthesia (93.3%-100.0%; 95% confidence interval for the difference of the success rates: -2.3% to 17.9%). No intergroup differences were observed in block-related pain scores and adverse events. The DI group required fewer needle passes (median ± interquartile range: 4 ± 2 vs 7 ± 3; P < 0.0001) as well as shorter needling (8.4 ± 2.9 vs 10.7 ± 2.7 minutes; P < 0.0001) and performance (9.0 ± 3.2 vs 11.2 ± 3.0 minutes; P = 0.001) times. CONCLUSION: Although DI and TII ultrasound-guided supraclavicular blocks seem to provide comparable success rates, we cannot exclude the possibility that an intergroup difference of 17.9% might have gone undetected. Due to its quick onset, the TII technique results in a shorter total anesthesia-related time.