Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment option for patients with acquired aplastic anemia (AA). However, in patients above 40 years of age the overall survival remains below 60% at 3 years (Giammarco et al, Blood 2018). We decided to investigate the impact of age and donor type on the outcome of patients with AA given HSCT in the decade 2011-2020. Methods All consecutive HSCT for acquired AA performed at EBMT centers between 2011 and 2020 were evaluated (inherited AA and second HSCT were excluded). Data were retrieved from the EBMT registry Promise, which includes detailed information about the underlying disease, HSCT procedure, and treatment outcomes, including engraftment, graft failure, acute and chronic graft-versus-host disease (GvHD), overall survival (OS), as well as GvHD/relapse-free survival (GRFS). Role of year of HSCT, age, donor type, interval from diagnosis, previous immunosuppressive treatment (IST), HSCT-comorbidity index and donor age on patient outcomes were investigated. Results A total of 3464 AA patients underwent HSCT in the decade 2011-2020 in 365 EBMT transplant centers, with a median follow up of 3.2 years (95% CI 3-3.3). Indications for BMT were moderate AA in 10.7%, severe AA in 61.8%, and very severe AA in 27.5% of patients. Median age at HSCT was 20.9 years (interquartile range 12.2-35.5), with proportion of patients aging <18, 18-40 and >40 years of 40.9%, 39.1% and 19.9%, respectively. Patients were transplanted either from an HLA-matched sibling (MSD; 51.2%), matched unrelated (MUD; 30.8%), mismatched-unrelated (MMUD; 9.8%) or mismatched haplo-identical (Haplo; 8.2%) donor. Three- and five- OS were 81% and 80%; globally, with a better 3-year OS in HSCT performed in the second quinquennium (83% vs 79%, p<0.001). In MVA, period of HSCT (2016-2020 vs 2011-2015, HR 0.63; p<0.001), age (reference <18; HR 1.54 for 18-40, 2.41 for 41-50, 2.80 for 51-60 and 3.93 for >60; each p<0.001), donor type (reference MSD; HR 1.26 for MUD [p=0.04], 2.10 for MMUD [p<0.001] and 4.20 for Haplo [p<0.001]), interval from diagnosis (cut-off at 6 months, HR 1.24; p=0.03), HSCT-comorbidity index (HR 1.39 and 1.56 for intermediate and high risk; p=0.01 and <0.001) and donor age (p<0.001) all impacted OS. For patients with available information (n=930) about previous IST, 3-year OS was affected by year of HSCT (2016-2020, HR 0.65, p=0.01), age (HR 2.37 for 51-60 [p=0.001] and 2.84 for >60 [p<0.001]), and donor type (HR were 2.38 for MMUD and 2.63 for Haplo, both p<0.001), but not interval from diagnosis or previous IST. In MSD recipients, estimates of 3-year OS were 93%, 87%, 69%, 71% and 59% in patients <18, 18-40, 41-50, 51-60 and >60 (p<0.001). The same estimates were 89%, 81%, 76%, 64% and 65% in MUD recipients (p<0.001), 78%, 66%, 76%, 48% and 61% in MMUD recipients (p=0.003), and 67%, 62%, 50%, 52% and 15% in Haplo recipients (p<0.001). Recipient age did not impact on neutrophil engraftment, graft failure (primary or secondary) or acute GvHD, while it significantly affected platelet engraftment (p=0.007), chronic GvHD (p<0.001) and GRFS; instead, donor type affected all neutrophil and platelet engraftment (p=0.031 and p<0.001), primary and secondary graft failure (p=0.003 and p<0.001), acute and chronic GvHD (p<0.001 for both) and GRFS. Estimates of 3-year GRFS according to age (<18, 18-40, 41-50, 51-60 and >60) were 73%, 68%, 61%, 54% and 53%; 3-year estimates of GRFS according to donor type (MSD, MUD, MMUD and Haplo) were 73%, 65%, 58% and 54%, respectively (p<0.001). Investigating cause of death at 3 years, recipient age affected infectious mortality (6%, 8%, 14%, 22% and 22 in <18, 18-40, 41-50, 51-60, >60; p<0.001), but not mortality from GvHD or other specific causes. Conclusion We showed that HSCT outcome improved in recent years, and that age and donor type continue to be the most important factors affecting OS after HSCT for AA, mostly due to infectious mortality. However, the age threshold driving HSCT mortality largely depend on donor type. Indeed, survival rates meaningfully decline in recipient >60 for MSD, >50 for MUD and MMUD, and >40 for Haplo. Nevertheless, prospective studies are needed to guide treatment decisions.