After heart valve surgery, due to the persistence of foreign bodies in the heart and endocardial damage, platelets and fibrin are easily deposited on the endocardium and prosthetic materials, and when transient bacteremia occurs, pathogens may remain and proliferate here, forming an unwieldy flora that eventually leads to infective endocarditis (IE). IE is a very dangerous disease, especially in prosthetic valve infective endocarditis, where the mortality rate can exceed 50%. Therefore, the prevention of IE has become an important issue after valve surgery. As early as the 1950s, the American Heart Association (AHA) recommended the prophylactic application of antibiotics before invasive procedures/examinations (including dentistry, gastrointestinal tract, genitourinary system, etc.) to reduce the risk of IE. However, to date, there has not even been a large randomized controlled study in this area, making this strategy more of a “concept” than a reliable evidence base. The guidelines for the prevention and treatment of IE published in Europe and the United States in recent years point out that transient bacteremia caused by random events in daily life is the most important cause of IE, while IE caused by invasive operations in dentistry, gastrointestinal tract and genitourinary system is far less frequent than expected; and question the strategy of using antibiotics in advance to prevent IE, arguing that in most cases, even if antibiotics do play a preventive role, it is difficult to compensate for the side effects of the drugs themselves. In most cases, even if antibiotics do prevent IE, it is difficult to compensate for the harm caused by the side effects of the drugs themselves. On this basis, the guidelines reflect this transmutation of understanding with a marked change in the indications for prophylactic antibiotic application. The need for prophylactic antibiotics prior to non-cardiac surgery/operation depends on an assessment of both the patient and the surgical operation. Patients who do not have significant IE risk factors do not require antibiotics prior to non-cardiac surgery. The term “risk factors” refers not only to the fact that certain populations are more susceptible to IE, but more importantly, that the clinical consequences of IE, if it occurs, may be more severe. By this definition, all patients who undergo heart valve surgery (including valve replacement and plasty surgery) are at the highest risk for IE. The size of the procedure and the magnitude of the injury are undoubtedly closely related to the occurrence of IE. According to the latest guidelines, various endoscopic examinations of the gastrointestinal and genitourinary systems, such as colposcopy and cystoscopy, do not require prophylactic antibiotics, but if there is an obvious infection at the examination site and the subject is at high risk for IE, prior anti-infective treatment is necessary. Various obstetrical and gynecological surgeries or operations, including curettage, abortion, spontaneous delivery or cesarean section, and cathartic hysterectomy, are still controversial in different guidelines, but considering our national conditions and health care conditions, we still recommend the prophylactic application of antibiotics. The choice of prophylactic and perioperative antibiotics depends first of all on the type of dominant flora at the surgical site and should also take into account the common pathogenic species of IE. Experience in Europe and the United States shows that the perioperative effects of Enterococcus spp. on IE should be taken into account during gastrointestinal and genitourinary surgery. Among them, Enterococcus faecalis (Enterococcus faecalis) is the predominant causative agent, accounting for 90% of enterococcal IE, and Enterococcus faecium (Enterococcus faecium) and others are much less pathogenic. Enterococci are resistant to antibiotics and may require a combination of bactericidal agents for a longer period of time (up to 6 weeks) for complete killing; at the same time, drug-resistant strains of enterococci are more common and can be resistant to a variety of antibiotics including aminoglycosides, β-lactams, and even vancomycin. Therefore, both the US ACC/AHA guidelines and the European ESC guidelines recommend the combination of broad-spectrum penicillin (e.g., ampicillin or hydroxyampicillin) and aminoglycosides (e.g., gentamicin) for infection prevention in the perioperative period; for those allergic to β-lactams, vancomycin combined with gentamicin can be used as a prophylactic strategy. The timing of prophylactic application of antibiotics is consistent with the general principles of preoperative dosing to prevent and control incisional infections, which are administered 30 minutes before the start of the surgical operation.