Adaptive servo-ventilation (ASV) therapy is a novel modality of noninvasive positive pressure ventilation and is now widely utilized to treat patients with chronic heart failure (CHF). However, there has been no clinical study of the effect of ASV therapy on readmission and cost-effectiveness for the treatment of CHF. The present study was conducted to evaluate the clinical efficacy and cost-effectiveness of home ASV therapy in 45 patients with a history of two or more admissions a year for worsening CHF. Seven patients refused to undergo chronic ASV therapy and three died. Thus, 35 patients were eventually enrolled in the present study. New York Heart Association class (2.8 ± 0.4 versus 2.3 ± 0.5, p < 0.001), log plasma B-type natriuretic peptide level (2.53 ± 0.44 versus 2.29 ± 0.40 pg/mL, p < 0.0001), left atrial dimension (47.5 ± 7.0 versus 44.9 ± 7.6 mm, p = 0.014), and mitral regurgitation area ratio (20.3 ± 12.1 versus 16.9 ± 8.9%, p = 0.007) decreased significantly after 12 months of ASV therapy. The frequency of hospitalization after ASV was significantly lower than before ASV (1.0 ± 1.0 versus 2.3 ± 0.5 times/year/patient, p < 0.0001). ASV also decreased the duration of hospitalization from 64.4 ± 46.5 to 22.8 ± 27.5 days/year/patient (p < 0.0001). Consequently, the total medical costs were reduced by 37% after ASV (1.95 ± 1.37 versus 3.11 ± 1.75 million yen/patient, p = 0.003). ASV therapy reduced readmissions and medical costs in patients with CHF.