Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) ineligible for allogeneic stem cell transplantation. Recently, rabbit ATG with cyclosporine A has been used as a first-line IST regimen in patients with SAA because of unavailability of horse ATG. We retrospectively analyzed adult SAA patients who were treated with horse ATG (n=46) or rabbit ATG (n=53) between Feb 2001 and May 2010 to compare hematologic response and survival. Overall response rates at 3, 6, 12, and 18 months were similar in both the horse and rabbit ATG groups: 28.3 versus 35.8 % (P=0.421), 39.1 versus 45.3 % (P=0.537), 45.7 versus 49.1 % (P=0.735), and 47.8 versus 50.9 % (P=0.757), respectively. The complete response (CR) rate at 6 months in the horse ATG was significantly superior in comparison with the rabbit ATG (13.0 versus 1.9 %, P=0.031). But CR rates became similar in both groups after 6 months: 17.4 versus 11.3 % (P=0.387) at 12 months and 21.7 versus 22.6 % (P=0.914) at 18 months. Lymphocyte depletion after ATG was more profound and protracted in the rabbit ATG group compared to the horse ATG group. Overall survival (P=0.460) and failure-free survival (P=0.911) were not significantly different between the two groups. Our retrospective study demonstrated that the efficacy of first-line IST with rabbit ATG is similar to that with horse ATG. However, the time from treatment to CR was longer with rabbit ATG than with horse ATG, partly due to more profound and protracted lymphocyte depletion.