Background: Left ventricular assist systems (LVASs) are essential for modern management of end-stage heart failure, and provide longer survival and improved quality of life. However, infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients who have received an LVAS is a common complication and associated with elevated mortality. Linezolid (LZD) is an oxazolidinone antibiotic with a broad spectrum of activity against Gram-positive organisms including MRSA. Treatment of LVAS-related infections with LZD in Japanese patients has not been reported. The purpose of this study was to investigate the efficacy and safety of LZD in patients implanted with an LVAS. Methods: The medical records of patients who underwent LVAS implantation from April 2004 to December 2010 were retrospectively reviewed. We analyzed type of infection, responsible microorganism, outcome, and adverse events of LZD treatment. Thrombocytopenia was defined as a decrease in platelet count of >25% and anemia as a decrease in hemoglobin level of >2 mg/dl. Results: During the study period, 62 patients underwent LVAS implantation, with LVAS-related MRSA bloodstream infection (BSI) identified in 11 [8 males, 3 females; mean age, 32.0±12.7 years (range, 16-59 years)], all of whom received an extracorporeal Nipro-Toyobo® device and were supported for a mean duration of 820 days (range, 518-1519 days). The mean duration of initial therapy with LZD was 13.3±5.5 days (range, 8-24 days). Adverse events following initial treatment associated with LZD occurred in 10 patients (thrombocytopenia in 7, anemia in 4, anorexia in 7), though they were controlled with careful management in all cases. Vancomycin or teicoplanin was given to all patients after treatment of LZD ended. LZD therapy was repeatedly provided for 10 of the patients, and the numbers of re-treatment ranged from 1 to 12 and administration periods were from 11 to 687 days (mean, 95 days). Seven patients underwent heart transplantation and none had an LVAS-related infection identified after that procedure. Conclusion: LZD treatment with careful management may be beneficial for patients with LVAS-related MRSA BSI.