Limited data are available describing donor adverse events (AEs) associated with filgrastim mobilized peripheral blood stem cell (PBSC) collections in unrelated volunteers. We report results in 2408 unrelated PBSC donors prospectively evaluated by the National Marrow Donor Program (NMDP) between 1999 and 2004. Female donors had higher rates of AEs, requiring central line placement more often (17% vs 4%, P< .001), experiencing more apheresis-related AEs (20% vs 7%, P< .001), more bone pain (odds ratio [OR]=1.49), and higher rates of grades II-IV and III-IV CALGB AEs (OR=2.22 and 2.32). Obese donors experienced more bone pain (obese vs normal, OR=1.73) and heavy donors had higher rates of CALGB toxicities (>95 kg vs <70 kg, OR=1.49). Six percent of donors experienced grade III-IV CALGB toxicities and 0.6% experienced toxicities that were considered serious and unexpected. Complete recovery is universal, however, and no late AEs attributable to donation have been identified. In conclusion, PBSC collection in unrelated donors is generally safe, but nearly all donors will experience bone pain, 1 in 4 will have significant headache, nausea, or citrate toxicity, and a small percentage will experience serious short-term adverse events. In addition, women and larger donors are at higher risk for donation-related AEs.