Background: Several regional anesthesia (RA) techniques have been described for distal upper limb surgery. However, the best approach in terms of RA block success rate and safety is not well recognized. Objective: To assess and compare the surgical anesthesia and efficacy of axillary brachial plexus block with other RA techniques for hand and wrist surgery. The attainment of adequate surgical anesthesia 30 min after block placement was considered a primary outcome measure. Additionally, successful block outcomes were required without the use of supplemental local anesthetic injection, systemic opioid analgesia, or the need to convert to general anesthesia. Methods: We performed a systematic search in the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and CENTRAL. RCTs comparing axillary blocks with other brachial plexus block techniques, distal peripheral forearm nerve block, intravenous RA, and the wide-awake local anesthesia no tourniquet (WALANT) technique were included. Results: In total, 3070 records were reviewed, of which 28 met the inclusion criteria. The meta-analysis of adequate surgical anesthesia showed no significant difference between ultrasound-guided axillary block and supraclavicular block (RR: 0.94 [0.89, 1.00]; p = 0.06; I2 = 60.00%), but a statistically significant difference between ultrasound-guided axillary block and infraclavicular block (RR: 0.92 [0.88, 0.97]; p < 0.01; I2 = 53.00%). Ultrasound-guided infraclavicular blocks were performed faster than ultrasound-guided axillary blocks (SMD: 0.74 [0.30, 1.17]; p < 0.001; I2 = 85.00%). No differences in performance time between ultrasound-guided axillary and supraclavicular blocks were demonstrated. Additionally, adequate surgical anesthesia onset time was not significantly different between ultrasound-guided block approaches: ultrasound-guided axillary blocks versus ultrasound-guided supraclavicular blocks (SMD: 0.52 [-0.14, 1.17]; p = 0.12; I2 = 86.00%); ultrasound-guided axillary blocks versus ultrasound-guided infraclavicular blocks (SMD: 0.21 [-0.49, 0.91]; p = 0.55; I2 = 92.00%). Conclusions: The RA choice should be individualized depending on the patient, procedure, and operator-specific parameters. Compared to ultrasound-guided supraclavicular and infraclavicular block, ultrasound-guided axillary block may be preferred for patients with significant concerns of block-related side effects/complications. High heterogeneity between studies shows the need for more robust RCTs.