We report a fatal case of native valve endocarditis due to Mycobacterium abscessus in a hemodialysis patient. The diagnosis was based on culture isolation of acid-fast bacilli from peripheral blood and a permanent catheter tip, and their identification as M abscessus by a reverse hybridization-based assay and direct DNA sequencing of the 16S-23S internal transcribed spacer region. Rapid diagnosis and combination therapy are essential to minimize mortality due to this pathogen. Although combination therapy was started with clarithromycin and tigecycline, the patient refused to take clarithromycin due to severe abdominal pain. The patient became afebrile after therapy with tigecycline alone although bacteremia persisted. He was discharged against medical advice and readmitted three months later for persistent fever. His blood cultures again yielded M abscessus and a transesophageal echocardiogram showed two mobile vegetations. The patient was noncompliant with therapy and died due to cardiac arrest and multiorgan failure. This report shows that M abscessus should also be considered in the differential diagnosis of infective endocarditis in hemodialysis patients.