Background and Objectives The treatment of acquired aplastic anemia (AA) is based on allogeneic bone marrow transplantation (BMT) and immunosuppressive therapy. The aim of this study was to assess the outcome of children and adults with AA treated in the last decade, and to determine whether results have improved in two sequential time periods: 1991–1996 and 1997–2002. Design and Methods We studied 2479 consecutive patients with AA, classified according to first-line treatment, BMT (n= 1567) or immunosuppressive therapy (n= 912), and stratified according to two sequential time periods. Analyses included variables related to the patients, disease and transplant. Results The actuarial 10-year survival was 73% and 68% for patients treated with BMT or immunosuppression, respectively (p= 0.002). BMT outcome improved significantly with time (69% and 77%, p= 001) for both matched sibling donor (MSD)(74% and 80%; p= 0.003) and alternative donor (38% and 65% p= 0.0001) transplants, and was better in children (79% versus 68%, p< 0.0001). In multivariate analysis favorable predictors (p< 0.001) were younger age, transplant after 1996, a MDS, ashort diagnosis-transplant interval, and no irradiation. There was no significant improvement over time for patients receiving immunosuppressive therapy (69% and 73% p= 0.29). Survival was significantly better in children (81% versus 70%, p= 0.001), especially in those with severe AA (83% versus 62%, p= 0.0002). Combined immunosuppression was superior to single drug treatment (77% versus 62%, p= 0.002). In multivariate analysis significant predictors of survival following immunosuppressive treatment were age≥ 16 years (p= 0.0009), longer interval between diagnosis-treatment (p= 0.04), and single drug versus combined immunosuppression (p= 0.02). Interpretation and Conclusions Outcome has improved in subsets of AA patients: those receiving first-line BMT and children with very severe AA treated with immunosuppression. Age remains a major predictor of outcome following both treatments. Early intervention is associated with a significantly better outcome and is strongly recommended, whatever the firstline therapy.