Ventricular free wall rupture (VFWR) is the second most common cause of death in patients with acute ST-elevation myocardial infarction (STEMI). Nevertheless, few reports have investigated the factors, including different treatment strategies, associated with VFWR in Taiwanese patients. Therefore, the aim of this study was to compare the risk of VFWR in Taiwanese patients with acute STEMI who had received primary percutaneous coronary intervention (PCI), rescue PCI, scheduled PCI, thrombolytic therapy, and pharmacologic treatment. In this medical records review study, records of patients with acute STEMI admitted to a regional hospital in south Taiwan between March 1999 and October 2013 were screened. Multivariate stepwise logistic regression analysis was used to evaluate the association between the risk of VFWR and its independent factors. The overall incidence of VFWR among the 1545 patients with acute STEMI in this study was 1.6%. Compared with primary PCI, the risk of VFWR was significantly higher in patients who had received thrombolysis (adjusted odds ratio = 6.83, P = 0.003) or pharmacologic treatment alone (adjusted odds ratio = 3.68, P = 0.014). The risk of VFWR in patients receiving rescue PCI or scheduled PCI was not significantly different from that in patients receiving primary PCI. In addition, older age and Killip class >I were associated with an increased risk of VFWR in patients with acute STEMI, whereas the use of angiotensin-converting enzyme inhibitors was associated with a lower risk of VFWR. In conclusion, findings from this medical record review study provide support for the use of primary PCI, rescue PCI, and scheduled PCI over thrombolytic therapy and pharmacologic treatment in reducing the risk of VFWR in Taiwanese patients with acute STEMI.