Delayed platelet engraftment is a major complication of umbilical cord blood (CB) transplantation. Megakaryocytes derived from CB in vitro are smaller than megakaryocytes derived from bone marrow (BM) or mobilized peripheral blood from adults. Small megakaryocyte size may contribute to delayed platelet engraftment. To test whether small size persists after transplantation, we measured megakaryocyte size, concentration, and maturational stage in BM biopsy specimens obtained after transplantation in archived BM samples from patients receiving CB (CB group, n = 10) versus mobilized peripheral blood or BM transplantation (BM group, n = 9). Megakaryocytes in the postengraftment BM samples were significantly smaller in the CB group than in the BM group (median diameter, 16.7 vs 22.0 microm). There were no significant differences in megakaryocyte concentration or maturational stage between the CB and BM groups. For the first time, we demonstrate that the attainment of adult size in CB-derived megakaryocytes is delayed after human CB transplantation.