Background Nucleated cell yields of marrow harvests depend on factors related to donors, the procedure itself, and the volume of marrow harvested. Few attempts have been made to relate donor characteristics to harvest volume. We hypothesize that the percentage of total donor blood volume accessed for harvesting impacts the nucleated cell yield per ml of marrow collected. Methods and Materials We investigated 481 consecutive unrelated marrow harvests from a single center. Donor characteristics including weight, body mass index (BMI), white blood cells (WBCs), hemoglobin (Hgb), and platelet counts, as well as estimated total blood volume, were recorded and compared with nucleated cell yields and harvest volumes. Results The percentage of donor blood volume accessed for marrow harvesting was inversely related to nucleated cell yields (r = −0.57). The donor–recipient weight differential impacted cell yields as well (r = 0.35), with heavier recipients requiring increased marrow volumes from smaller donors to satisfy their nucleated cell needs. 3.73 × 108/kg of recipient weight could be collected with 95% certainty when harvest volumes did not exceed 16.1% of donor total blood volume. In a stepwise multiple regression analysis, 45.4% of cell yield variance was explained by blood volume percentage accessed for harvesting, donor weight, and WBC. Donor sex, BMI, and platelet counts did not contribute further to cell yield variance. Smokers had higher cell yields than nonsmokers (20.4 vs. 18.3 × 106/ml; 95% confidence interval 0.62, 3.47) independent of other parameters. Conclusion Establishing the relationship between percentage of estimated donor total blood volume and recipient cell needs can facilitate donor selection for successful hematopoietic cell (HPC) transplants.