<p>Hematopoietic stem cell transplantation is a well-established therapy for hematological malignancies, with cryopreservation enabling long-term storage of peripheral blood stem cells (PBSCs). Although generally safe, technical complications during cryopreservation and thawing can compromise product integrity. Among these, fibrin clot formation post-thaw is rare, but may have implications for product infusion and engraftment. We report here two cases where clot was observed in the cryopreserved product post thaw, and an elaborate root cause analysis was performed in both the cases. Root cause analysis identified multiple potential contributors, including patient-related factors, monocyte activation, cryofibrinogens, adequacy of anticoagulation, and autologous plasma use in the cryopreservation mixture. The engraftment was unaffected in both cases, and no infusion related adverse events occurred in both the cases. Preventive measures were reinforced, emphasizing optimized anticoagulation during apheresis, plasma reduction where feasible, validated cryoprotectant use, standardized thawing protocols, and staff retraining. This case underscores that fibrin clot formation in cryopreserved PBSC products, though rare, requires vigilance and careful management. Clot formation however did not affect engraftment and outcome of the patient. No adverse events were reported following infusion.</p>