Objectives We aimed to improve the limitations encountered in previously published studies and then compare mortality in patients with acute myocardial infarction (AMI) who were treated with either fibrinolysis or a primary percutaneous coronary intervention (PPCI). Methods EMBASE, MEDLINE, and the Cochrane databases were searched for trials comparing fibrinolysis with PPCI in patients with AMI. The only endpoint that was assessed in this analysis was all-cause mortality. Therefore, in-hospital, short-term, mid-term, and long-term mortality were analyzed, whereby odds ratios (OR) with 95% confidence intervals (CIs) were calculated using the RevMan 5.3. Results A total of 11 429 patients obtained from 37 studies (involving 27 trials) were included. The results of this analysis showed that fibrinolytic therapy was associated with significantly higher in-hospital and mid-term mortality (OR: 0.61; 95% CI: 0.46-0.82, P=0.001 and OR: 0.73; 95% CI: 0.54-0.99, P=0.04, respectively). Short-term and long-term mortality were also significantly higher in the fibrinolytic group (OR: 0.76; 95% CI: 0.65-0.90, P=0.001, and OR: 0.82; 95% CI: 0.71-0.96, P=0.01, respectively) compared with PPCI. Conclusion This analysis of 11 429 patients showed a significantly higher mortality rate to be associated with fibrinolysis compared with PPCI in these patients with AMI. Hence, compared with fibrinolysis, PPCI is expected to be the preferred method of revascularization in patients with AMI, especially in PCI-capable centers. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.