IMPORTANCE Surgical procedures can be performed in different settings, but the association between the operative setting and patient safety and cost to the patient and payer is unknown. OBJECTIVE To examine differences in complications, total payments, and out-of-pocket (OOP) spending for minor hand surgical procedures performed in office, ambulatory surgery center (ASC), and hospital outpatient department (HOPD) operative settings. DESIGN, SETTING, AND PARTICIPANTS A retrospective, population-based cohort study was conducted using deidentified claims data from private employer-sponsored health insurance from January 1, 2009, to December 31, 2017. Patients aged 18 years or older undergoing carpal tunnel release, trigger finger release, excision of wrist ganglion, and excision of small hand masses (N = 468 365) were included. EXPOSURES Operative setting, defined as procedures performed in the clinic setting, ASC, and HOPD. MAIN OUTCOMES AND MEASURES Complications during the 90-day postoperative period, total payments (total facility and payer reimbursement), and OOP spending.