Introduction Stenotrophomonas maltophilia is an environmental bacterium increasingly involved in nosocomial infections and resistant to most antibiotics. It is important to recognize and efficiently treat infections with this bacterium as soon as possible. Case presentation We present a case of Stenotrophomonas maltophilia prosthetic valve endocarditis secondary to an indwelling catheter infection. The patient was cured without surgery. We review other cases of S. maltophilia endocarditis from the literature and describe the peculiarities of this case. Conclusion S. maltophilia endocarditis is a rare disease that is often hospital-acquired and related to an indwelling catheter infection. The high lethality is likely related to the intrinsic resistance of nosocomial bloodstream infections to commonly prescribed antibiotics.