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Background and Objectives: ICMR conducted a multicentric trial “PLACID” that allowed COVID convalescent plasma (CCP) as an experimental drug for the management of moderate COVID-19 disease and the authors' institute was one of the participating centers. The efficacy of CCP in COVID-19 is still debatable. However, unlike therapeutic efficacy, there is not enough literature on issues and challenges faced by health-care institutions in donor recruitment, and the entire vein-to-vein process and approach of CCP transfusion. The authors would like to share their experiences, challenges faced, and their mitigation during the course of donor recruitment, screening, testing, apheresis donation, storage, inventory management, and issue and transfusion of CCP including the regulatory provisions, as their evolution. Methods: This retrospective study was conducted over a period of 7 months at a large tertiary care hospital in north India. Based on ICMR guidelines, the study analyzed the screening process and donation from all consecutive potential CCP donors. The study also identified various issues and challenges faced by the institute and how they were resolved. Results: Prospective donors registered at the blood center were 843. Majority were males (96.6%), first-time CCP donors (93%), age interval 31–45 years (52.2%), who had a history of mild COVID-19 symptoms (86.9%), and were home-quarantined (83.8%). The most common blood group was B positive (50.6%). Only 6.3% of donors were deferred due to the absence of anti-COVID-19 antibodies. Of 843, 705 selected CCP donors donated 1488 CCP units and six donors (0.8%) experienced mild adverse reactions. Challenges faced by authors included donor recruitment, lack of regulatory approval for plasmapheresis, revisions of COVID-specific selection criteria, no “anti-COVID-19 antibody” kit, and CCP inventory management. Conclusion: This study provides real-world comprehensive data on process management of CCP donors and their donations. This understanding of the process, its challenges, and their mitigation could be a template for any possible future pandemic.