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Key Clinical Message: Vincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID‐19 vaccination. Our case report highlights the need for further research to establish standard management guidelines for COVID‐19‐vaccine‐associated ITP. Adult immune thrombocytopenia (ITP) can occur as a rare complication following several viral infections or a rare adverse event or complication of vaccination. In this paper, we report a case of a 39‐year‐old male patient with severe refractory ITP that began 4‐weeks after receiving his third (booster) dose of the COVID‐19 vaccine (BNT162b2, Pfizer‐BioNTech). He was given oral dexamethasone 40 mg daily for 4 days followed by prednisone at 1 mg/kg (85 mg daily) for 10 days. In the following weeks, we attempted several other lines of therapy to treat his ITP, including anti‐RhD immunoglobulin, which, unfortunately, caused moderate hemolysis requiring packed red blood cell transfusion, intravenous immunoglobulin (given at a subtherapeutic dose of 0.4 g/kg for only 1 day since it was not available), rituximab, and eltrombopag. The patient, unfortunately, showed no response to any of these treatments. This was an indicator to initiate salvage therapy with vincristine 2 mg weekly for 3 weeks. The patient's platelet count started to increase remarkably during the third week of vincristine and normalized after 4 weeks. We review the findings, clinical characteristics, and management approaches that were reported in the literature regarding COVID‐19‐vaccine‐induced ITP. More in‐depth research is needed to delineate standard guidelines for the management of such cases. This report underscores the importance of resorting to vincristine and eltrombopag as great options for severe and refractory ITP related to the COVID‐19 vaccine. [ABSTRACT FROM AUTHOR]