Although primary percutaneous coronary intervention (PCI) in clinical trials has lower rates of reinfarction, stroke and mortality than fibrinolytic therapy, because of system delays in routine practice, field triage and prehospital administration of fibrinolytic therapy may lead to similar clinical outcomes, especially in those patients who present in the first 2 h after symptom onset. Necessary for these outcomes is the liberal use of both rescue PCI and in-hospital revascularisation. Non-invasive prediction of failed reperfusion may be enhanced by the use of ST recovery, patient characteristics and troponin T levels, measured by point-of-care assays. This review focuses on the timing of, and indications for, an invasive strategy after fibrinolytic therapy, including that for failed pharmacological reperfusion.