Objective: To compare the efficacy of a fully oral intensive regimen versus the classic immunosuppressive regimen in patients with aplastic anemia (AA) who were unsuitable for antithymocyte globulin (ATG) therapy. Methods: 93 AA patients ineligible for ATG treatment were selected as the research subjects. They were divided into Group A (n=44) and Group B (n=49) based on their treatment regimens. Group A patients were treated with a full oral intensified regimen [cyclosporine + androgen + thrombopoietin receptor agonist (TPO-RA)], Group B patients were treated with a classic immunosuppressive regimen (cyclosporine + androgen), both group were treated for a duration of 6 months. The efficacy indicators (detachment from transfusion rate, overall hematological response rate, complete remission rate), blood routine index levels, and incidence of adverse reactions were compared between the two groups. Results: At the 3 month of treatment, the platelet and red blood cell transfusion rates in group A were higher than those in group B (P < 0.05). At the 6 month of treatment, the overall hematological response rate and complete remission rate in Group A were higher than those in Group B (P<0.05). The complete remission rate in Group A was higher than that in Group B (34.09% vs. 12.24%, P<0.05). The neutrophil, hemoglobin, platelet, and reticulocyte levels in Group A were higher than those in Group B (P<0.05). There was no statistically significant difference in the occurrence of adverse reactions between the two groups(P>0.05). Conclusion: For AA patients unsuitable for ATG, the fully oral intensive triple therapy significantly improved hematologic responses, accelerated transfusion independence, and enhanced blood count recovery compared to the classic dual therapy, without increasing the risk of short-term severe adverse events.