This multicenter international retrospective analysis aimed to evaluate the efficacy and safety of subcutaneous alemtuzumab (ALZ) as an alternative immunosuppressive therapy for aplastic anemia (AA). The study included 57 with AA patients who received ALZ treatment in four centers in Brazil and the United Kingdom. Most patients had severe aplastic anemia (SAA). The median age of the patients was 52 years, with 21% being older than 65 years. Out of the 60 ALZ treatments analyzed, 57% were first-line treatments, 26% were second-line, and 17% were administered after at least two lines of therapy. At 6 months, the overall response rate (ORR) was 54%. At 12 months, the ORR increased to 57%, with a complete response rate of 18% and a partial response rate of 39%. The cumulative incidence of response was significantly higher in patients younger than 65 years (68%) and in those who received a 103 mg subcutaneous ALZ dose (61%). The overall survival (OS) rates were 84% at 1 year and 71% at 4 years. OS at 4 years was significantly higher in patients who responded to ALZ treatment (hazard ratio: 9.88, 95% confidence interval 2.12 - 46.0, p = 0.004). Adverse events associated with ALZ were mostly of low grade, and infectious events were infrequent. In conclusion, subcutaneous ALZ appears to be a feasible, effective, and safe alternative to horse antithymocyte globulin (hATG) in patients with aplastic anemia who require immunosuppressive treatment. This is particularly relevant for centers and countries with limited access to hATG.