Clinical and angiographic correlates of ischemia-driven target vessel revascularization (ITVR) in patients undergoing primary percutaneous coronary interventions (PCI) are currently less well known. Accordingly, we examined 2,981 patients enrolled in different Primary Angioplasty in Myocardial Infarction trials, who underwent primary PCI to evaluate risk factors and outcomes of individuals requiring subsequent ITVR. At 6 months, ITVR was required in 321 patients (11%). Compared to the cohort without ITVR, patients requiring ITVR were younger (P=0.036), females (P=0.018), and more likely to have systolic blood pressure >100 mmHg on presentation (P=0.022), family history of premature coronary artery disease (P=0.035), and postprocedure dissection (P=0.001). In contrast, Killip Class >I on presentation (P=0.05), left circumflex as infarct-related artery (P=0.022), and the use of ticlopidine (P=0.044) and stents (p=0.057) were less frequent among ITVR patients. Multivariate analysis identified younger age (for each 10-year decrease, odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06-1.32), female gender (OR: 1.41, 95% CI: 1.05-1.89), and final dissection (OR: 1.69, 95% CI: 1.23-2.33) as independent risk factors for ITVR. In-hospital reinfarction (P < 0.001) was increased and at 6 months remained higher in ITVR patients; in-hospital and 6-month mortality did not differ between the two groups. Our study identifies the incidence, risk factors, and outcomes of patients requiring ITVR after primary PCI. Importantly, our data suggest that no increase in mortality occur, if ITVR is promptly performed to treat recurrent ischemia after primary PCI.