Objective To summarize the clinical treatment experience of blood culture-negative infective endocarditis,and to explore the surgery chance and therapeutic strategy of blood culture-negative endocarditis. Methods One hundred and sixty-six patients who were diagnosed blood culture-negative endocarditis in the Aisa Heart Hospital of Wuhan from Jul. 2008 to Dec. 2012 were recruited in the study. Broad-spectrum antibiotics including cefuroxime axetil and levofloxacin were used before the result of blood culture,and sensitive antibiotics were selected to control patient's condition when getting the result of blood culture. But broad-spectrum antibiotics were continuously used to the blood culture-negative endocarditis until stable condition. When the conditions were stable,active preparation before surgery should be carried out. Thoroughly clear the vegetation and protect the cardiorespiratory function during operating. Kata-step antibiotics were used to control patient's condition until normal temperature,as well as the number of leukocytes decreased,blood sedimentation normalized and C-reaction protein decreased. Then,the narrow-spectrum antibiotics were selected including cephalosporin until discharged from hospital,and continued treatment of antibiotics for 4 - 6 weeks. Results Five patients died after the operation,including 1 case died of low cardiac output syndrome,2 cases died of multiple organ failure,1 case died of septicemia and the 1 case died of cerebral embolism. All the other patients discharged from hospital successfully. Conclusion The patients with blood culture-negative IE should be controlled rapidly. The duration and dose of antibiotics should be enough. Active operative preparation should be taken and then surgery timely. Thus,the hospital mortality could decrease and prompt the long-term outcome.