We compared serious early and late events experienced by 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors who underwent collection of PBSC or BM between 2004 and 2009 as part of a prospective study through the National Marrow Donor Program. Standardized FDA definitions for serious adverse events (SAEs) were used, and all events were reviewed by an independent physician panel. BM donors had an increased risk for SAEs (2.38%for BMvs 0.56%for PBSC; odds ratio [OR], 4.13; P < .001), andwomen were twice as likely to experience an SAE (OR for men, 0.50; P 5 .005). Restricting the analysis to life-threatening, unexpected, or chronic/disabling events, BM donors maintained an increased risk for SAEs (0.99% for BM vs 0.31% for PBSC; OR, 3.20; P < .001). Notably, the incidence of cancer, autoimmune illness, and thrombosis after donation was similar in BMvs PBSC donors. In addition, cancer incidence in PBSC donorswas less than that reported in the general population (Surveillance, Epidemiology, and End Results Programdatabase). In conclusion, SAEs after donation are rare butmore often occurred in BM donors and women. In addition, there was no evidence of increased risk for cancer, autoimmune illness, and stroke in donors receiving granulocyte colony-stimulating factor during this period of observation.