Despite recent clinical trials of percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction, specific groups of patients that may benefit from adjunctive or alternative therapy have yet to be adequately characterized. The in-hospital outcome of 151 consecutive patients treated for acute myocardial infarction with urgent PTCA of the infarct-related artery wa studied to identify a subgroup of patients at high risk. Patients were divided into two groups based on the angiographic presence of either single-vessel (n = 86) or multivessel (n = 65) coronary artery disease. Despite PTCA of only the infarct-related artery and similar baseline clinical characteristics such as age, peak serum creatine kinase concentration, left ventricular ejection fraction, and time from the onset of chest pain to arrival at the hospital, the group with multivessel disease had a lower rate of successful angioplasty (75% vs 92%, p < 0.005), with higher incidences of persistent total occlusion of the infarct-related artery (14% vs 3%, p < 0.02) and procedural complications during PTCA (28% vs 13%, p less-than-or-equal-to 0.02), and were more likely to have multiple complications (12% vs 1 %, p < 0.004). In addition, the group with multivessel disease had a higher rate of urgent (less-than-or-equal-to 24 hours) coronary artery bypass graft surgery (13% vs 2%, p < 0.05) and a trend toward a higher in-hospital mortality rate (6% vs 1 %, p less-than-or-equal-to 0.17). By stepwise logistic regression, only the presence of single-vessel versus multivessel disease was predictive of PTCA success (p < 0.005). The location of the infarct-related artery was not associated with any differences in outcome. We conclude from these data that urgent PTCA of the infarct-related artery only as treatment for acute myocardial infarction has a lower success rate and higher associated risk in patients with multivessel disease. This may be due to their greater ischemic burden and/or a fundamental biochemical or pathologic difference in the involved lesions. Thus in patients with multivessel coronary artery disease, alternative revascularization, improved mechanical hemodynamic support, or both may be warranted to achieve a better success rate and reduce complications and mortality.