Many patients with acute ischaemic stroke have contraindications to thrombolytic therapy. We describe a 45 yr old Afro-Caribbean female with HbSC disease whom was electively admitted for a cerebral angiogram to evaluate an intracavernous aneurysm measuring 20 mm in diameter. During the procedure, she suffered a right MCA territory ischaemic event with a NIHSS of 10. A CT angiogram demonstrated no dissection and no evidence of a major vessel occlusion. Tissue plasminogen activator (tPA) was administered intravenously within 60 minutes of symptom onset. She had clinical and haematological evidence of a painful sickle cell crisis and required manual exchange transfusion within a few hours of thrombolysis. This is the first reported case of the use of thrombolysis for acute stroke in a sickle cell crisis; and in the presence of such a large unruptured aneurysm. A registry of unusual thrombolysis cases might help clinicians in cases when there is little evidence to support decision-making.