Patients and physicians may defer unrelated donor hematopoietic cell transplantation (HCT) as curative therapy because of the mortality risk associated with the procedure. Therefore, it is important for physicians to know the current outcomes data when counseling potential candidates. To provide this information, we evaluated 15,059 unrelated donor hematopoietic cell transplant recipients between 2000 and 2009. We compared outcomes before and after 2005 for 4 cohorts: age <18 years with malignant diseases (n = 1920), ages 18 to 59 years with malignant diseases (n = 9575), ages ≥ 60 years with malignant diseases (n = 2194), and nonmalignant diseases (n = 1370). Three-year overall survival in 2005 to 2009 was significantly better in all 4 cohorts (<18 years: 55% versus 45%, 18 to 59 years: 42% versus 35%, ≥60 years: 35% versus 25%, nonmalignant diseases: 69% versus 60%; P < .001 for all comparisons). Multivariate analyses in leukemia patients receiving HLA 7/8 to 8/8–matched transplants showed significant reduction in overall and nonrelapse mortality in the first year after HCT among patients who underwent transplantation in 2005 to 2009; however, risks for relapse did not change over time. Significant survival improvements after unrelated donor HCT have occurred over the recent decade and can be partly explained by better patient selection (eg, HCT earlier in the disease course and lower disease risk), improved donor selection (eg, more precise allele-level matched unrelated donors) and changes in transplantation practices.