OBJECTIVETo describe an outbreak of severe Group A Streptococcus (GAS) infections that appeared to be associated with use of a biologic dermal substitute on foot woundsDESIGNRetrospective cohort study of cases and similar uninfected patientsSETTING/PATIENTSPatients attending the podiatry clinic at a Veterans Affairs Medical Center between July 2011 and November 2011INTERVENTIONSMicrobiology laboratory data were reviewed for the calendar year, a case definition was established and use of the biologic dermal substitute was discontinued. Staff were cultured to identify potentially colonized employees. A case–cohort study was designed to investigate risk factors for disease. Emm typing and pulsed field gel electrophoresis (PFGE) were performed to identify strain similarity.RESULTSIn 10 months, 14 cases were identified, and 4 of these patients died. All strains were emm type 28 and were identical according to PFGE. Discontinuation of biologic dermal substitute use halted the outbreak. A prior stroke was more common in the case cohort vs uninfected patient cohorts. The number of patients attending the clinic on 13 probable transmission days was significantly higher than on nontransmission days. We identified 2 patients who were present in the clinic on all but 1 probable transmission day. Surveillance cultures of podiatry clinic staff and cultures of the same lot of retained graft material were negative.CONCLUSIONSA carrier was not identified, and we believe the outbreak was associated with inter-patient transmission likely due to lapses in infection control techniques. No additional cases have been identified in >3 years following the resumption of dermal substitute use in May 2012.Infect. Control Hosp. Epidemiol. 2016;37(3):306–312