OBJECTIVES: In the evaluation of healthcare interventions, systematic review and meta-analysis of randomized controlled trials (RCTs) has been regarded as the highest level of evidence. However, these methodologies have limitations that are inherent to potential bias and heterogeneity that may be present in the source data. In addition, meta-analyses can constitute a form of sequential analysis as in principle a new systematic review can be conducted each time trial is conducted. This study seeks to demonstrate the implications for the consideration of findings of statistical significance from meta-analysis via an examination of RCT and meta-analyses findings of intracoronary with intravenous abciximab in ST-elevation myocardial infarction (STEMI) patients. METHODS: A systematic review of RCTs and meta-analyses. Data on mortality were pooled using: (1) cumulative meta-analysis, which does not take into consideration potential false-positive findings ude to repeatd significance tests as new trials are addded; and (2) sequentail meta-analysis, which allows for the possibility that the meta-analysis was repeated after each trial was published. RESULTS: To date, the efficacy and safety of intracoronary versus intravenous administration of abciximab in STEMI patients has been evaluated in eight RCTs, and ten systematic reviews and meta-analyses. None of the trials, with the exception of one, reported significant benefits associated with intracoronary abciximab; this is consistent with the findings reported by a recent large trial. Meta-analyses carried out prior to the publication of this recent trial showed contrasting results. However, the sequential analysis did not indicate a statistically significant reduction in mortality at any point. CONCLUSIONS: It is also important to take into account the essentially sequential nature of the meta-analysis. The total number of trial that will be conducted is not fixed, and we should allow for the fact that multiple meta-analyses may be conducted, although not always reported, as trials are conducted.