Background Regional anesthesia has proven to be a highly effective technique for pain control after total shoulder arthroplasty. However, concerns have been raised about the safety of upper-extremity nerve blocks, particularly with respect to the incidence of perioperative respiratory and neurologic complications, and little is known about their influence, if any, on length of stay after surgery. Questions/purposes Using a large national cohort, we asked: (1) How frequently are upper-extremity peripheral nerve blocks added to general anesthesia in patients undergoing total shoulder arthroplasty? (2) Are there differences in the incidence of and adjusted risk for major perioperative complications and mortality between patients receiving general anesthesia with and without nerve blocks? And (3) does resource utilization (blood product transfusion, intensive care unit admission, length of stay) differ between groups? Methods We searched a nationwide discharge database for patients undergoing total shoulder arthroplasty under general anesthesia with or without addition of a nerve Each author certifies that he or she, or a member of his or her immediate family, has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. The institution of one of the authors (SGM) has received, during the study, funding from the Anna-Maria and Stephen Kellen Physician-Scientist Career Development Award provided by the Hospital for Special Surgery. One or more of the authors (RR, YLC, XS, MM) has received, during the study,