Antisynthetase syndrome (ASS) is characterized by inflammatory muscle disease, pulmonary and joint involvement, and antisynthetase autoantibodies, with anti-Jo-1 antibody being the most common. Despite the use of immunosuppressive drugs, the prognosis of lung involvement seems poor. Herein, we report a case of refractory ASS, which maintained long-term remission by double filtration plasmapheresis (DFPP) combined with immunosuppressive therapy. For a 65-year-old woman, who was diagnosed with ASS, immunosuppressive therapy was initiated and plasmapheresis (PP) was performed five times due to acute interstitial pulmonary disease and inflammatory myopathy. She remained in remission for eight months following PP. Increase in interstitial involvement was identified by lung tomography when the patient presented again with complaint of progressive increase in dyspnea and muscle pain. Although the immunosuppressive therapy was increased for the patient with elevated creatine phosphokinase (CPK) (2776 IU/mL), a rapid decrease in diffusion capacity of the lung for carbon monoxide (DLCO) was observed and the patient underwent PP. After four sessions of therapy, insufficient clinical and laboratory response was obtained (control CPK 1797 IU/mL) and because of that issue DFPP using a 2A filter was performed to the patient. There was a marked improvement in complaints of the patient, DLCO, and laboratory findings (control CPK 508 IU/mL) after three sessions of DFPP. The patient, who continued the immunosuppressive therapy after DFPP procedure, is being followed for 12 months in remission. Although our experience is limited with only one patient, DFPP seems promising as a treatment option for ASS with severe lung involvement. J. Clin. Apheresis, 28:422-425, 2013. (c) 2013 Wiley Periodicals, Inc.