Pretreatment blood counts, particularly the absolute reticulocyte count (ARC) ≥25×109/L, correlate with response to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). In recent trials, eltrombopag (EPAG) combined with standard IST yielded superior responses than did IST alone. Our single institution retrospective study aimed to elucidate whether historical response predictors associated with IST plus EPAG. We sought correlations of blood counts, thrombopoietin levels and the presence of paroxysmal nocturnal hemoglobinuria clones with both overall and complete responses in 416 patients with SAA, aged 2-82 years (median, 30 years), initially treated with IST plus EPAG between 2012 and 2019 (n=176) or with IST alone between 1999 and 2010 (n=240). Patients in the group of overall responders to IST plus EPAG, compared to non-responders, had significantly higher pretreatment ARC, higher neutrophil counts and reduced thrombopoietin levels, as also observed for IST alone group. Addition of EPAG markedly improved the overall response in subjects with ARC between 10-30×109/L from from 60% (54 of 90) to 91% (62 of 68). Absolute lymphocyte count (ALC) correlated with complete response in both IST with and without EPAG, especially in adolescents and adults aged ≥10 years, but the correlation was reversed in younger children. Platelet count and the presence of a paroxysmal nocturnal hemoglobinuria-clone did not correlate with IST-responses. Blood counts remain the best predictors of response to nontransplant therapies in SAA. In comparison to IST alone, addition of EPAG, patients with lower ARC were now included in the better prognosis category.