e20513 Background: Patients with Multiple Myeloma (MM) are at risk for developing sepsis due to defective humoral immunity, underlying disease factors like renal failure, iron overload, and treatment with immunosuppressive agents. Sepsis is a significant cause of morbidity and mortality in patients with MM. In this study, we aimed to study trends of inpatient outcomes and health care burden of patients with sepsis in MM. Methods: Adult patients with MM admitted to the hospital from 2012 to 2017 were identified from the Nationwide Inpatient Sample database and were stratified into two groups based on the diagnosis of sepsis. Multivariate regression analysis was used to adjust for confounders when calculating for mortality. Statistical tests for trends of mortality, length of stay and hospital charges were performed. Results: A total of 513,615 patients with MM met the inclusion criteria. Sepsis was found to be the most common cause of admission amongst these patients (12.2%) and of the patients with MM who died in the hospital, 38.1% carried the primary diagnosis of sepsis. Mean age of the patients was 70.1 years and they were predominantly Caucasian (62.1%) with male preponderance (57.7%). MM patients admitted with sepsis were found to have higher mortality (15.7 and 3.5% P < 0.0001),higher hospital costs (22,082$ vs 15,206; P < 0.0001) and longer hospital stays (8.1 days vs 6.0 P < 0.0001) when compared to those admitted for other reasons. Temporal trends have been noted to improve over the years, with mortality decreasing from 18% to 13.1%, (p trend < 0.001). Length of stay (in days) decreased from 8.3 to 7.7 days (p trend = 0.009) and hospital charges (in dollars) decreased from 22,407 to 21,209 (p trend < 0.001). Conclusions: Although the improving trends are promising, sepsis still continues to be significantly contributing to morality and morbidity in patients with MM. Measures to identify the changing spectrum of infectious diseases, their predisposing risk factors along with strategies to recognize and prevent early stages of sepsis could have a significant impact on lowering mortality and health care burden. [Table: see text]