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Matthew W Konigsberg, John D Mueller, Jordan A Lebovic, R Kumar Kadiyala Department of Orthopedic Surgery, Columbia University Medical Center, New York, NY, USACorrespondence: Matthew W KonigsbergDepartment of Orthopedic Surgery, Columbia University Medical Center, 622 W. 168th St. 11th Floor, New York, NY 10032, USATel +1-212-305-5976Fax +1-212-305-6193Email Mk3294@cumc.columbia.eduIntroduction: The purpose of this study was to describe four cases of patients who developed concomitant upper extremity and gluteal compartment syndrome in the context of substance abuse. In somnolent patients unable to provide a reliable physical exam, the healthcare provider must be aware of patients presenting with concomitant upper extremity and gluteal compartment syndrome.Methods: Retrospective chart review identified cases of the combined upper extremity and gluteal compartment syndrome following illicit drug abuse at a single academic center during the years 2009– 2019.Results: During the 11-year period examined, a total of eight patients were diagnosed with compartment syndrome secondary to illicit drug use and prolonged immobilization. Four (50%) patients presented with combined upper extremity and gluteal compartment syndrome. All of these patients underwent prompt surgical release of the affected compartments. All eventually returned to normal activities of daily living.Discussion: Compartment syndrome is primarily a clinical diagnosis, with physical exam being extremely important. In patients presenting with somnolence secondary to illicit drug use, physical exam may not be reliable. It is critical to have a high clinical suspicion in this patient population, understanding that these patients may present with concomitant upper extremity and gluteal compartment syndrome.Level of Evidence: Level IV, case series.Keywords: compartment syndrome, fasciotomy, trauma, upper extremity, gluteal