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Background Despite advances in diagnosis and management, infective endocarditis (IE) is associated with considerable morbidity and mortality. Given the emergence of drug- resistant organisms, it is unclear whether this has impacted the characteristics and outcomes of IE among intravenous drug users (IDUs) and non-IDUs. Methods We conducted a single center retrospective cohort study. 306 records of hospitalized adults diagnose with IE by ICD-9/ICD-10 codes were identified from 2011 to 2018. 244 patients met criteria. IRB approval was obtained. The baseline demographic, microbiologic, echocardiographic variables and outcomes were extracted from the chart, and compared between IDUs and non-IDUs. Results 112 (45.9%) patients were IDUs and significantly younger (mean age 36 vs. 64, p< 0.001). Both methicillin-sensitive (44.6% vs. 23.5%, p< 0.001) and methicillin-resistant (29.5% vs. 13.6%, p= 0.002) Staphylococcus aureus associated IE were more prevalent in IDUs compared to non-IDUs. Streptococcus species (22.7% vs 11.6%, p=0.02), excluding Enterococcus species, and coagulase-negative Staphylococcus (12.1% vs 1.8%, p=0.002) were significantly more prevalent in non-IDUs. IE in IDUs were more likely to have tricuspid valve vegetations (56.3% vs. 13.6%, p< 0.001), whereas non-IDUs were more likely to have mitral valve (39.4% vs. 25%, p=0.02) and aortic valve vegetations (46.2% vs. 15.2%, p< 0.001). 19% of patients with IE underwent valve replacement within 6 months, and 17% died within 90 days. A multivariable model that included age, gender, and IDU status, age was the only variable that remained independently associated with 90-day mortality (adjusted OR 1.031; 95% CI 1.006, 1.057; p< 0.01). Conclusion In this single-center experience, we found that methicillin-sensitive Staphylococcus aureus was the dominant organism among IDUs and non-IDUs. We also found that methicillin-resistant Staphylococcus aureus was significantly more prevalent among IDUs with IE. Provably related to an increase prevalence of colonization with resistant organisms in the community. Despite the shift in prevalence of methicillin-resistant Staphylococcus aureus among IDUs, there was no increased 90-day mortality risk after adjustment for age and gender. Disclosures All Authors: No reported disclosures