Recent studies reported that a costoclavicular block (CCB) can consistently block almost all the branches of the brachial plexus while sparing the phrenic nerve and provide effective analgesia after shoulder surgery. We aimed to compare the efficacy of the CCB used as a sole blocking technique for shoulder surgery compared with the interscalene block (ISB).212 patients undergoing elective arthroscopic shoulder surgery were randomized to receive an ISB or a CCB based on a non-inferiority design. All patients received titration sedation with propofol under monitored anesthesia care during surgery. Primary outcomes were the proportion of patients with complete motor blockade of the suprascapular nerve (SSN) and the incidence of the hemidiaphragmatic paralysis (HDP). Secondary outcomes included block-related variables, complications, postoperative pain scores, etc.The proportion of patients with complete motor blockade of SSN at 20 min between CCB and ISB group (53% vs 66%) exceeded the predefined non-inferiority margin of -5%, but were comparable at 30 min (87% vs 91%). CCB resulted in a significantly lower incidence of HDP than that in ISB group (7.55% vs 92.45%), as well as the incidence of Horner's syndrome (0% vs 18.87%) and dyspnea (0% vs 10.38%). None of the patients experienced failed blocks or conversion to general anesthesia. Pain scores were comparable between the groups.Compared to the ISB, ultrasound-guided CCB may be a comparable technique with less unfavorable complications for high-risk patients undergoing arthroscopic shoulder surgery.