Radiocontrast media-induced acute severe thrombocytopenia is a very rare complication and potentially life-threatening. Here, we report the case of a 63-year-old male patient with severe acute thrombocytopenia following first exposure to intravenous non-ionic contrast media without immediate allergic reactions. His platelet count dropped from 107000/μL to 2000/μL after six hours of radiocontrast infusion. After administration of corticosteroid and transfusion of platelet concentrates, the platelet count returned gradually to normal within 5 days. To the best of our knowledge, non-ionic contrast media-induced isolated acute severe thrombocytopenia following no signs or symptoms of immediate allergic reaction has never been described.