Purpose To determine the cumulative prevalence of septic arthritis presenting to the emergency department of an academic medical center and evaluate the use of clinical data to diagnose infection versus inflammation. Methods We conducted a records review of a single institution with 80,000 annual emergency room visits. We included a consecutive series of patients with suspected wrist infection from January 1, 2007, to December 31, 2008. Adults complaining of atraumatic wrist pain with either erythema or swelling on physical examination or a final diagnosis of septic arthritis, gout, pseudogout, cellulitis, wrist hematoma/edema, or wrist arthritic flare were suspected to have infection. We collected data using a standardized data abstraction form. Results We reviewed 804 patient records. A total of 104 patients meeting inclusion criteria for suspected wrist joint infection during the 2-year study period were included. Mean age was 62.5 years (SD, 20.2 y); 63 were men. There were 12 patients with a history of gout, 4 with a history of pseudogout, and 19 with a history of diabetes. Wrist arthrocentesis was performed in 31 patients, and 11 underwent surgical treatment. There were 16 patients with a final diagnosis of gout, 11 with pseudogout, 43 with cellulitis, 13 with upper extremity hematoma/edema, and 15 with wrist arthritic flare. The cumulative prevalence of septic arthritis was 5%. Conclusions In this series of emergency department patients with suspected wrist joint infection, gout, pseudogout, and cellulitis were the most common etiologies. The cumulative incidence of septic wrist arthritis was low. © 2011 American Society for Surgery of the Hand. All rights reserved.