A modified high-dose cyclophosphamide (HD-CTX) plus cyclosporine (CsA) regimen was adopted for severe/very severe aplastic anemia (SAA/VSAA) patients, and the effectiveness was compared with that of antithymocyte globulin (ATG) plus CsA regimen. A total of 121 patients enrolled in this study received either CTX plus CsA (CTX group, 48 cases) or ATG plus CSA (ATG group, 73 cases). The early death rate was 4.2% in CTX group and 8.2% in ATG group, showing no significant difference (p=0.312). The total response rate in CTX group and in ATG group was 54.2% and 57.5% at 3 months, 64.6% and 72.6% at 6 months, and 72.9% and 78.1% at 12 months, respectively (p>0.05). The overall 5-year survival rate was 81.2% and 80.7%, and the event free survival rate was 68.2% and 67.3% in CTX and ATG groups, respectively (p>0.05). The total medical cost of CTX group was 54.8% less than that of ATG regimen (p=0.000). In summary, treatment of SAA/VSAA with CTX plus CsA has comparable effectiveness to conventional regimen and less cost.