Stenotrophomonas Maltophilia (previously known as Xanthomonas maltophilia and Pseudomonas maltophilia ) is an aerobic, nonfermenting, gram-negative bacillus, which has emerged as a serious nosocomial pathogen in patients with compromised immunity. It is a rare cause of endocarditis with only 20 cases previously reported in medical literature. The risk factors associated with S maltophilia endocarditis include intravenous drug abuse, dental treatment, previous cardiac surgery, and infected intravascular devices. S maltophilia is resistant to multiple antibiotics, which leads to frequent therapeutic failures. Although the optimal antibiotic treatment for S maltophilia endocarditis remains unknown, most of the patients received 2 or more antibiotics. We report a case of S maltophilia endocarditis of prosthetic aortic valve, associated with a painless aortic dissection, that responded well to a combination of ciprofloxacin and chloramphenicol. The literature is reviewed to elaborate the disease characteristics, the treatments used, and the prognosis of the S maltophilia endocarditis.