© 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Objective: To assess the health care burden of septic arthritis in the U.S. and examine the associated factors. Methods: We used the U.S. Nationwide Emergency Department Sample (NEDS) data of patients hospitalized with septic arthritis as the primary diagnosis from 2009–12 to assess time-trends. Multivariable-adjusted models assessed demographics, comorbidity and hospital characteristics as potential predictors of duration of hospitalization, total hospital (inpatient and ED) charges and discharge to home. Results: In 2009, 2010 and 2012 in the U.S., respectively, there were 13,087, 13,662 and 13,714 hospitalizations with septic arthritis as the primary diagnosis. Respective average hospital stay was 7.4 vs. 7.4 vs. 7.2 days; total hospital charges were $601 vs. $674 vs. $759 million; and proportion discharged home were 43% vs. 43% vs. 44%. Almost 25% each were discharged to a skilled facility or with home health. Age >50 years, Medicaid and self-pay as primary payer, Northeast U.S. hospital location, teaching hospital status, heart failure and diabetes were associated with longer hospitalization; hyperlipidemia, hypertension or gout were associated with a shorter hospital stay. Similar associations were noted for higher hospital charges. Age >50 years, higher income, Medicare insurance, heart failure, diabetes and longer hospital stay were associated with lower odds, and Western U.S. hospital location and gout with higher odds, of discharge to home. Conclusions: We noted an increase in hospital charges from 2009–12, but no time trends in duration or outcomes of hospitalization for septic arthritis. Comorbidity associations with outcomes indicate the potential for developing interventions to improve outcomes.