Immunosuppressive therapy (IST) with antithymocyte immunoglobulin (ATG) or antilymphocyte immunoglobulin (ALG) and cyclosporine A (CsA) is the treatment of choice against severe aplastic anemia (SAA) worldwide. However, a comparison of the efficacy of porcine ALG (pALG) and rabbit ATG (rATG) as a first-line treatment for acquired SAA has not been reported. In the present study, we retrospectively analyzed SAA patients treated with either pALG (n = 43) or rATG (n = 32) and compared their hematologic responses and survivals. There were no significant differences in overall response (OR) rates between pALG and rATG groups at 3 months (OR 41.86 versus 40.62% (P = 0.914), 6 months (OR 66.67 versus 61.29% (P = 0.635), 9 months (OR 69.05 versus 61.29% (P = 0.490), or 12 months (OR 69.05 versus 64.51% (P = 0.684), respectively. The OR rates in patients with SAA or very severe aplastic anemia (vSAA) in both groups were similar after a 12-month treatment (pALG 74.07 versus 60.00%, P = 0.550; rATG 70.00 versus 54.55%, P = 0.640). Patients who experienced <30-day interval between diagnosis and treatment displayed higher OR rates (at 12 months) than those with intervals ≥30 days (pALG 83.33 versus 50.00%, P = 0.021; rATG 87.50 versus 40.00%, P = 0.006). There were no significant differences in 2-year overall survival (OS) between pALG (87.4 ± 6.2%) and rATG (83.2 ± 7.8%) (P = 0.493). Infection was the major cause of death in both groups. In summary, pALG + CsA showed similar efficacy as rATG + CsA, as a first-line treatment for acquired SAA.