Objectives Infective endocarditis (IE) with non-HACEK Gram-negative (GN) organisms is rare, but associated with poor outcomes. The purpose of this study was to quantify the microbiology, treatment strategies, and frequency of poor outcomes in patients with non-HACEK GN IE. Materials Retrospective cohort of adults with definite non-HACEK GN IE from 1/11-1/19. The primary endpoint was poor patient outcome, defined as a composite of all-cause death or infectionrelated readmission within 90-days of index infection. Results 43 patients were included: 51% patients were men, and the median (IQR) age was 40 (31-50) years. Forty patients reported injection drug use. The most common organisms were Pseudomonas aeruginosa (68%) and Serratia marcescens (9%). Seventy-six percent of patients received definitive combination therapy; the most common antibiotics used in combination with a β-lactam were aminoglycosides (50%) and fluoroquinolones (34%). Three patients discontinued combination therapy due to toxicity. Twelve-month, all-cause mortality and readmission was 30% and 54%, respectively. In multivariable logistic regression, variables independently associated with composite poor outcome were receipt of fluoroquinolone-based IE combination therapy and septic shock. Conclusions Long-term mortality and readmission rates were high. Patients who received fluoroquinolone-based IE combination therapy more frequently developed poor outcomes than those who did not.