Rabbit antithymocyte globulin (rATG) was proven effective as salvage therapy for refractory aplastic anemia (AA), or for relapse after initial therapy with horse ATG (hATG). Several clinical trials were performed to assess the efficiency of rATG as a first-line therapy for AA patients; however, their results were variable. The aim of the present study was to assess hematologic response and survival in severe AA (SAA) and very severe AA (VSAA) patients treated with rATG and cyclosporin A (CsA) in our center. The factors involved in these outcomes were also explored. A total of 292 patients with newly diagnosed, acquired SAA or VSAA received a combination of rATG and CsA as first-line therapy, and the results were retrospectively assessed. The median age was 18 years (range = 2-73 years). The early death rate was 5.5%, and the total response rates were 49.0% (143 responders), 60.3% (176 responders), 65.8% (192 responders), and 68.5% (200 responders) at 3, 6, 9, and 12 months, respectively, after immunosuppressive therapy. In multivariate analysis, initial response to granulocyte colony-stimulating factor (G-CSF) was the predictive factor for response to therapy at 12 months. Median follow-up of surviving patients was 34 months (range = 0-117 months). Five-year overall survival was 83.2%, and the 5-year, event-free survival was 67.2%. Independent prognostic factors for overall survival were neutrophil count and achievement of any response following rATG therapy. Our results indicate that rATG/CsA is a safe and effective first-line treatment for SAA/VSAA.