Escherichia coli (E.coli) is a rare cause of endocarditis, although is a common causative agent of bacteremia. An 89-year-old woman presented with recurrent episodes of fever and persistent E. coli bacteremia with 3-month duration, despite antimicrobial therapy. At first, a urinary tract infection was diagnosed and later a mycotic aneurysm of the abdominal aorta was found and required an endovascular repair. The persistence of fever and the evidence of a systolic murmur at the mitral focus raised the suspicion of endocarditis. A transesophageal echocardiogram and a cardiac Magnetic Resonance Imaging (MRI) confirmed the presence of a vegetation at the mitral valve and the patient was treated with ceftriaxone. The presence of comorbid conditions and certain bacterial virulence factors predispose to this rare condition. A high level of suspicion is important to early diagnosis and prompt therapy.