Escherichia coli (E. coli) is a rare cause of infective endocarditis due to its lack of traditional virulence factors that promote endocardial adherence. Previous case reports of E. coli infective endocarditis demonstrate specific risk factors to include advanced age over 70, female sex, diabetes, immunosuppression, and intravascular or cardiac devices. Antecedent genitourinary infection is the most common source. We present a case of a 55-year-old Honduran man with a recent bioprosthetic mitral valve replacement and tricuspid valve repair who presented with one month of subjective fevers, night sweats, anorexia, and significant weight loss. After extensive work-up, the patient was diagnosed with E. coli infective endocarditis secondary to E. coli growth in blood cultures and a transesophageal echocardiogram (TEE) revealing a vegetation on his prosthetic mitral valve. An indolent gastrointestinal source was suspected to be the source of infection with imaging only notable for mild periappendiceal stranding concerning for a possible site of antecedent inflammation. He was treated with a 6-week course of ceftriaxone and gentamicin inpatient and then discharged on trimethoprim-sulfamethoxazole suppressive therapy with serial echocardiographic follow-up given the persistent small vegetation on repeat echocardiogram. Our case report and review of ten recent cases of prosthetic valve endocarditis described in the literature illustrates several common features of the epidemiology, presentation, and management of E. coli prosthetic valve endocarditis including more commonly reported non-genitourinary sources of bacteremia, a trend towards more frequent surgical interventions, and a declining mortality rate.