The addition of thrombopoietin receptor agonists (TPO-RAs) to immunosuppressive therapy (IST) improves the hematologic response rate and quality in patients with severe aplastic anemia (SAA). However, no studies have yet reported on whether there are differences in the efficacy of TPO-RAs. Here, we retrospectively analyzed the clinical data of SAA patients who received hetrombopag (HPAG) or eltrombopag (EPAG) as part of first-line standard IST to compare the efficacy. Sixty-seven patients were enrolled in the HPAG group and 42 patients in the EPAG group. The overall hematologic response (OR) rates of the HPAG group at 3 and 6 months after IST were 50.7% and 65.6%, respectively, close to that of the EPAG group (50%, p = 0.973; 73.8%, p = 0.494). The rates of complete response (CR) at 3 and 6 months were 13.4% and 31.3% in the HPAG group, respectively, which were like those in the EPAG group (11.9% and 28.6%), with no statistical difference (p = 1.00 and 0.59). The median time to first response (3.0 vs. 3.2 months, p = 0.79) was similar in HPAG and EPAG. The overall survival (OS) rates were 91.0% and 92.8% in the HPAG group and EPAG group (p = 0.53), respectively. Monosomy 7 was detected in one patient in the EPAG group and her disease transformed into acute myelocytic leukemia (AML) at 25 months after ATG treatment. One patient in HPAG had trisomy 8 at 9 months of ATG treatment, and bone marrow examination showed no disease progression. CONCLUSION: The addition of HPAG to standard IST in SAA patients showed similar response rates and response quality to that of EPAG. HPAG could be an alternative to EPAG for the first-line treatment of SAA patients.