Granulocyte-colony stimulating factor (G-CSF) mobilizes hematopoietic progenitor cells (HPC) into the peripheral blood. Donor peripheral blood platelet loss has been observed during both G-CSF mobilization and apheresis collection. This study evaluates two strategies to reduce donor platelet loss, preserve product CD34+ cell yield and collection efficiency and increase volume of whole blood (WB) processed. One hundred and two adults healthy donors were mobilized with either standard dose G-CSF (9.5–12 mcg/kg/day × 4 days) or lower dose G-CSF (7.5–10 mcg/kg/day × 4 days) according to their pre-mobilization platelet count. Apheresis centrifugal force was adjusted by lowering the packing factor (PF) setting on the apheresis instrument. Between-group differences were observed in absolute donor platelet loss (p = 0.04) favoring lower G-CSF dosing, while percent donor platelet loss trended towards significance (p = 0.10). Lowering PF from the manufacturer's default of 4.5 to 4.0 demonstrated between-group differences in absolute donor platelet loss (p < 0.05), percent donor platelet loss (p < 0.001), and apheresis product platelet content (p < 0.001). No differences were observed in the product CD34+ cell content and CD34+ cell collection efficiency when PF was reduced to 4.0. Additionally, a higher volume of WB could be processed due to reduced donor platelet loss. Together, these two strategies may mitigate the risk of cumulative platelet loss in G-CSF mobilized healthy donors undergoing apheresis collection, thereby increasing the likelihood of completing the target total blood volume to be processed while maintaining donor safety.