Prosthetic valve endocarditis (PVE) is a complication of valve replacement associated with high morbidity and mortality.Escherichia coli(E. coli) is rarely associated with infective endocarditis (IE), accounting for less than 1% of the cases reported. The low frequency is attributed to the organism’s low affinity to adhere to the endocardial endothelium. Risk factors that may play a role in developing IE byE. coliinclude age above 70, diabetes mellitus, a genitourinary source of infection, female sex, healthcare contact, implanted endovascular devices, and immunosuppression. We present a 70-year-old Hispanic woman who arrived with constitutional symptoms and persistent urinary complaints. She had diabetes mellitus, recurrent urinary tract infections, and native mitral valve IE treated with antibiotic therapy and tissue valve replacement. The valve was replaced with a mechanical valve a second time due to malfunctioning. The patient was found to haveE. colibacteremia and ultimately diagnosed with PVE. She was treated solely with ceftriaxone and gentamicin combination therapy resulting in complete resolution of valve vegetations. Our case represents the 11th report of this uncommon disease and illustrates its epidemiology and associated risk factors. We summarize the previous 10 cases reported and highlight the lack of prospective trial data to define optimal therapy for managing PVE caused byE. coli.