Aspirin and clopidogrel are used widely as antiplatelet agents due to their efficacy, safety, and tolerability. In rare cases, these agents can cause thrombotic thrombocytopenic purpura, but no report has documented severe thrombocytopenia in response to both drugs in the same patient. A 73-year old female developed severe thrombocytopenia following treatment with clopidogrel. Platelet count recovered within 6 months of drug withdrawal without additional thrombopoietic therapies. Seven months after the last dose of clopidogrel, thrombocytopenia recurred on aspirin therapy. Again, platelet count rebounded gradually and independently. This case suggests that some patients who experience thrombocytopenia in response to one antiplatelet agent may react similarly to other antiplatelet agents.