Background: In this study, we performed the infraclavicular block with combined ultrasound guidance and neurostimulation to selectively target cords to compare the success rates of placing a single injection of local anesthetic either in a central or peripheral location. Methods: Two hundred eighteen patients were enrolled in a consecutive, prospective study. Patients were randomized to injection of local anesthetic either centrally (posterior cord) or peripherally (medial or lateral cord) using ultrasound guidance and neurostimulation. Supervised senior anesthesiology residents or attending anesthesiologists performed the blocks. Both intent-to-treat and treatment-received analyses were used to compare central and peripheral placement efficacy. Results: The overall success rate was significantly higher for the central placements than peripheral placements (96% vs 85%, P = 0.004). Individual cord success rates were as follows: posterior 99%, lateral 92%, and medial 84% (P = 0.001). The central group required attending physician intervention more frequently (27% vs 6%, P < 0.001). Postoperative pain scores of ≤3 were more likely with central placement (100% vs 94%, P = 0.012). Conclusion: Central placement of a single injection of local anesthetic targeted at the posterior cord resulted in a higher success rate for infraclavicular block. Copyright © 2010 International Anesthesia Research Society.