Thrombolytic therapy for myocardial infarction may contribute to bleeding complications when central venous or arterial access is required, but peripheral venous access is usually uncomplicated. We report a patient in whom tissue plasminogen activator and subsequent intravenous heparin exacerbated bleeding from a disrupted intravenous access site, leading to acute compartment syndrome requiring surgical decompression. This case emphasizes the risks associated with iatrogenic trauma during thrombolytic therapy.