Although stent thrombosis has been greatly reduced by adequate stent expansion with high-pressure balloon inflations and by the use of antiplatelet drugs, this event is still frightening, as it may lead to acute myocardial ischemia resulting in acute myocardial infarction or sudden death. Therefore, the definition of factors associated with stent thrombosis may provide a better understanding of the mechanisms underlying this phenomenon and may permit us to define therapeutic strategies to further reduce its occurrence. The purpose of this study was to assess factors responsible for the occurrence of stent thrombosis after coronary stent implantation in 939 consecutive patients enrolled in the Registro Impianto Stent Endocoronarico (R.I.S.E. Study Group). Consecutive patients undergoing coronary stent implantation at 16 medical centers in Italy were prospectively enrolled in the registry. Clinical data, and qualitative and quantitative angiographic findings were obtained from data collected in case report forms at each investigator site. The study group consisted of 781 men and 158 women with a mean age of 59 yr: 1,392 stents were implanted in 1,006 lesions and expanded at a maximal inflation pressure of 14.7 +/- 3 atm. The great majority of patients (92%) received only antiplatelet drugs after coronary stenting. During hospitalization there were 45 major ischemic complications in 39 patients (4.2%): 13 events were related to acute or subacute thrombosis (1.4%). Another stent thrombotic event occurred in the first month of follow-up. On multivariate logistic regression analysis, stent thrombosis was related to the following factors: unplanned stenting (OR 3.46, 95% CI 1.65-7.23), unstable angina (OR 3.37, 95% CI 1.11-10.14) and maximal inflation pressure (OR 0.83, 95% CI 0.75-0.93). In conclusion, this registry shows that in an unselected population of patients undergoing coronary stenting, stent thrombosis occurs in less than 2% of patients and is significantly related to unplanned stent implantation, unstable angina, and maximal inflation pressure. The incidence of this phenomenon is likely to be further reduced by the use of new potent antiplatelet drugs, such as platelet glycoprotein IIb/IIIa antagonists.