Infective endocarditis (IE) is a critical and potentially fatal disease that requires bactericidal antibiotics. The most commonly pathogens of IE include streptococcus, staphylococcus, enterococcus and HACEK organisms (Haemophilus, Aggregatibacter, Actinomycetemcomitans, Cardiobacteriumhominis, Eikenellacorrodens and Kingellakingae) and the like. Streptococcus is the most common of them. The identity of the infecting organism and heart conditions associated with IE are very essential. Whether the patient’s heart valve has been replaced and the site of infected valves will affect subsequent treatment options, background information should be confirmed before treatment. Common IE treatment guidelines are published by the American Heart Association (AHA), European Society of Cardiology (ESC), the British Association of Antibacterial and Chemotherapy (BSAC) and the Sanford Guide, the last one is a significant reference in Taiwan. This article through a real patient who is a native valve streptococcal IE patient. We investigated the diagnostic criteria of IE and also explore the differences between guidelines through this case. He is a case of a 37-year-old male patient, who with a history of ventricular septal defect in the past. In addition to fever and a heart murmur, the other clinical manifestations are not obvious. Laboratory test data showed a tendency to inflammation, and blood culture test showed positive. Besides, his echocardiography also revealed that should be considered suffering from IE. After 4 weeks antibiotic treatment, his clinical condition was improved and blood culture test has been negative again. Because of the stable clinical condition, he finally discharged smoothly.