<p>Granulocytes are transfused to combat infections in neutropenic patients. Granulocytes are primarily collected through apheresis; however, the use of whole blood-derived buffy coats (BC) is on the rise as an alternative source for granulocyte transfusion. This study aimed to assess the differences in product characteristics and cost between BC granulocytes and apheresis granulocytes prepared at two tertiary care institutes in India. Between January 2013 and December 2022, we conducted a retrospective analysis of the operational considerations at two blood centers that prepared granulocyte concentrates using two different methods. In total, 321 apheresis granulocytes were collected at one institute, while 16,764 buffy coat (BC) granulocytes were prepared at another center. At the later facility, six individual BC bags from ABO-identical donors were processed simultaneously after receiving the request for transfusion. For apheresis donations, donor stimulation included steroids and G-CSF. The mean adult dose of granulocytes reported was 2.85 × 10¹⁰ for apheresis and 0.66 × 10¹⁰ for six units of BC granulocytes. There were significant differences in plasma volume, hematocrit, and platelet counts among the products prepared at the two centers (<i>p</i> &lt; 0.001). The center providing BC granulocytes reported shorter times from request to delivery than the center using apheresis products, but the average number of infusions required per patient was higher in the BC group. BC granulocytes have the potential to serve as an affordable alternative to apheresis granulocytes in resource-limited settings. However, the number of BC bags administered at a time needs to be optimized for achieving adequate doses.</p>