Scopulariopsis brevicaulis is a saprophytic fungus that commonly causes onychomycosis but rarely causes deep tissue infection. To the best of our knowledge, this is the first reported case of endocarditis caused by S. brevicaulis. The infection persisted despite two aortic valve replacements, debridement, and prolonged therapy with several antifungal agents. The patient eventually died due to an acute myocardial infarction caused by ongoing prosthetic valve endocarditis. We review case reports of deep tissue infections due to Scopulariopsis species.