The purpose of this article was to determine the incidence of in-stent thrombosis (IST) after coronary stent implantation in patients with cocaine abuse. A retrospective review was done of medical records of consecutive patients who underwent coronary stent implantation for obstructive coronary artery disease at a single inner-city institution from January 1997 to October 2006. Patients with temporal cocaine use were identified by positive urine drug screen. IST was confirmed angiographically. Of the 81 patients with active cocaine use that underwent coronary stent implantation, 4 (5%) suffered IST (mean period from stent implantation, 28.5 +/- 14 days). All procedures were performed successfully and received intravenous IIb/IIIa antagonist intraprocedurally. All patients were prescribed dual antiplatelet therapy with aspirin and clopidogrel at discharge; however, all 4 patients that suffered from IST continued cocaine abuse were noncompliant with the prescribed dual antiplatelet therapy. Of these 4 patients, 2 presented with ST segment elevation myocardial infarction (50%), whereas 2 presented with non-ST-segment elevation myocardial infarction (50%). One was managed medically. Two received repeat percutaneous coronary intervention, and 1 underwent coronary artery bypass surgery. The patient that underwent surgery died in the postoperative period. The remaining 3 patients survived. Patients with active cocaine abuse who undergo successful coronary stent revascularization have a high (5%) incidence of stent thrombosis. A majority of patients that suffer stent thrombosis continue cocaine abuse and are noncompliant with antiplatelet therapy.