BACKGROUND Acute ischemic stroke (AIS) is a rare but critical complication following ST-elevation myocardial infarction (STEMI). The risk of AIS or transient ischemic attack (TIA) may be amplified by invasive procedures, including primary percutaneous coronary intervention (PCI). This study aimed to investigate the factors associated with in-hospital AIS/TIA in patients with STEMI who required primary PCI. METHODS We included 941 STEMI patients who underwent primary PCI and divided them into an AIS/TIA group (n = 39) and a non-AIS/TIA group (n = 902), according to new-onset AIS/TIA. The primary interest was to find the factors associated with AIS/TIA by multivariate logistic regression analysis. We also compared clinical outcomes between the AIS/TIA and non-AIS/TIA groups. RESULTS The incidence of in-hospital deaths was significantly higher in the AIS/TIA group (46.2%) than in the non-AIS/TIA group (6.3%) (p < 0.001). Multivariate analysis revealed that cardiogenic shock (OR 3.228, 95% CI 1.492-6.986, p = 0.003), new-onset atrial fibrillation (AF) (OR 2.280, 95% CI 1.033-5.031, p = 0.041), trans-femoral approach (OR 2.336, 95% CI 1.093-4.992, p = 0.029), use of ≥4 catheters (OR 3.715, 95% CI 1.831-7.537, p < 0.001), and bleeding academic research consortium (BARC) type 3 or 5 bleeding (OR 2.932, 95% CI 1.256-6.846, p = 0.013) were significantly associated with AIS/TIA. CONCLUSIONS In STEMI patients with primary PCI, new-onset AIS/TIA was significantly associated with cardiogenic shock, new-onset AF, trans-femoral approach, the use of ≥4 catheters, and BARC type 3 or 5 bleeding. We should recognize these modifiable and unmodifiable risk factors for AIS/TIA in the treatment of STEMI.