Over the past few decades, several cardiac autoantibodies have been reported in sera from patients with dilated cardiomyopathy (DCM). Immunoadsorption (IA) therapy is one of the therapeutic tools to remove such autoantibodies. The objective of this study was to investigate functional effects of IA therapy using a tryptophan column in severe DCM patients. Of 49 patients enrolled, 44 were randomized from 10 sites in Japan. IA therapy was conducted in 40 patients with DCM (refractory to standard therapy for heart failure, New York Heart Association [NYHA] class III/IV, left ventricular ejection fraction [LVEF] <30%). Mean echocardiographic LVEF was significantly improved (23.8 ± 1.3% to 25.9 ± 1.3%, P = 0.0015). However, mean radionuclide LVEF over 3 months of IA therapy was not significantly improved (20.8 ± 1.1% to 21.9 ± 1%, P = 0.0605). The cardiothoracic ratio was also significantly decreased (P = 0.0010). NYHA functional class (P < 0.0001), subjective symptoms assessed by a quality of life questionnaire (P = 0.0022), maximum oxygen consumption (P = 0.0074), and 6-minute walk distance (P = 0.0050) were improved after IA therapy. Subgroup analysis revealed improvement of echocardiographic LVEF in patients with higher baseline autoantibody scores but not in those with lower scores. IA therapy improved subjective symptoms and exercise capacity in patients with refractory heart failure resulting from DCM. Favorable effect on cardiac function was noted in patients with higher autoantibody scores. J. Clin. Apheresis, 2016. © 2016 The Authors. Journal of Clinical ApheresisPublished by Wiley Periodicals, Inc.