Acute severe thrombocytopenia following contrast administration is incredibly rare, but it can lead to significant morbidity. This case details the experience of a 63-year-old male whose diagnostic coronary angiography quickly led to severe thrombocytopenia with cardiovascular compromise in the absence of any immediate symptoms of anaphylaxis. His platelet count normalized within a week, increasing from 2 × 103/μL to 328 × 103/μL. A thorough review of the literature along with the present case is being reported.