Background Patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolysis are increasingly, and ever earlier, referred for routine coronary angiography and where feasible, undergo percutaneous coronary intervention (PCI). We sought to examine the randomized clinical trials (RCTs) on which this approach is based. Methods We systematically searched EMBASE, Medline, and references of relevant studies. All contemporary RCTs (published since 1995) that compared systematic invasive management of STEMI patients after fibrinolysis with standard care were included. Relevant study design and clinical outcome data were extracted. Results Nine RCTs that randomized a total of 3320 patients were identified. All suggested a benefit from routine early invasive management. They were individually reviewed but important design variations precluded a formal quantitative meta-analysis. Importantly, several trials did not compare a routine practice of invasive management after fibrinolysis with a more selective 'ischemia-guided' approach but rather compared an early versus later routine invasive strategy. In the other studies, recourse to subsequent invasive management in the usual care group varied widely. Comparison of the effectiveness of a routine invasive approach to usual care was also limited by asymmetric use of a second anti-platelet agent, differing enzyme definitions of reinfarction occurring spontaneously versus as a complication of PCI, a preponderance of the 'soft' outcome of recurrent ischemia in the combined primary endpoint, and an interpretative bias when invasive procedures on follow-up were tallied as an endpoint without considering initial invasive procedures performed in the routine invasive arm. Conclusions Due to important methodological limitations, definitive RCT evidence in favor of routine invasive management following fibrinolysis in patients with STEMI is presently lacking.