Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. Methods: This is a retrospective, registry-based European Society for Blood and Marrow Transplantation study that investigates changes in patient- and transplant-related characteristics and posttransplant outcomes over time. Results: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18–78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p <.001), use of a haplo donor (from 4.6% to 26.4%; p <.001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p <.001). There was a significant decrease in total body irradiation and in vivo T-cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia-free survival (hazard ratio [HR], 0.79; p =.002) and overall survival (HR, 0.73; p <.001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p <.001) decreased over time. We also observed better graft-vs-host disease (GVHD) rates (acute GVHD II–IV: HR, 0.78; p =.03; GVHD-free, relapse-free survival: HR, 0.69; p <.001). Conclusions: Even in the absence of an MSD, outcomes of allo-HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD.