Infective endocarditis (IE) is a multisystem disease that results from infection, usually bacterial, of the endocardial surface of the heart. The main causative organisms of IE are gram-positive streptococci, staphylococci, and enterococci infection. Although Escherichia coli is among the most common causes of gram-negative bacteremia, IE due to this pathogen is rare. Here we report a case a 68-year-old female was presented with 10 days history of fever diagnosed with infective endocarditis according to Modified Duke Criteria where her blood culture isolated Escherichia coli organisms. On day two of admission, the patient developed an episode of atrial fibrillation, which was resolved with two stat doses of verapamil 2.5 mg. The patient was treated with intravenous cefotaxime 2 g 8 hourly. Intravenous antibiotics were continued for six weeks, and the patient had complete recovery without any complications.