Abstract Background The incidence of skin and soft-tissue infections (SSTIs), for which human immunodeficiency virus (HIV) is a significant risk factor, in United States emergency departments (EDs) increased dramatically after 2000 with the emergence of community-associated methicillin-resistant Staphylococcus aureus. Few studies have examined SSTI incidence among HIV-infected and non–HIV-infected patients in the United States after 2010. Methods Data were obtained for patient encounters at all academic medical center EDs affiliated with the Vizient clinical data warehouse assigned an SSTI-associated code based on the International Classification of Diseases, Ninth Revision, between 1 January 2009 and 31 December 2014. The rate was calculated per 1000 ED encounters by year and stratified by SSTI, HIV infection, or both, and by age group, race, payer type, and region of care. Poisson regression was used to assess temporal change over the study period. Results In 2009–2014, a total of 47317 HIV-associated and 820440 SSTI-associated encounters were recorded among 25239781 ED patient encounters. The rate of SSTIs decreased by 8% among all patients and by 14.6%, among those with HIV infection. The SSTI incidence overall decreased from 32.0 to 29.7 per 1000 ED encounters between 2009 and 2014. HIV-infected patients had a significantly higher rate of SSTIs than HIV-uninfected patients (adjusted rate ratio, 1.91; 95% confidence interval, 1.84–1.99). Conclusions The decline in SSTI incidence in US EDs between 2009 and 2014 is a remarkable epidemiologic shift from the increase in SSTIs after 2000, and further research is necessary to assess reasons for this decrease.