The aim of this study was to test the safety and efficacy of a novel rapid desensitization procedure in patients with acetylsalicylic acid sensitivity and coronary artery disease who underwent cardiac catheterization and coronary stent implantation. Aspirin plays a key role in the secondary prevention of atherothrombotic events and thrombotic complications after stent implantation. Aspirin sensitivity not only limits patients to benefit from the long-term use of this antiplatelet agent but is also often an impediment to the implantation of bare-metal and drug-eluting coronary stents. Of 1,014 patients admitted for cardiac catheterization, 26 (2.6%) had histories of aspirin sensitivity characterized by respiratory or cutaneous manifestations (none had previous anaphylactic reactions); of these, 61.5% presented with acute coronary syndromes. All patients underwent a novel rapid desensitization challenge procedure before cardiac catheterization, except for those presenting with ST-elevation myocardial infarctions (n = 4), who underwent desensitization before hospital discharge. The desensitization procedure involved the oral administration of 6 sequential doses of aspirin (1, 5, 10, 20, 40, and 100 mg) over 5.5 hours without the use of corticosteroids or antihistamines. Patients were followed for 1 year to assess compliance with aspirin therapy and adverse events. The desensitization procedure was successful in 23 patients (88.5%). Percutaneous coronary intervention with stent implantation was performed in 22 patients (1.8 stents/patient). Drug-eluting stents were used in all patients except those who underwent primary percutaneous coronary intervention (n = 3), in whom bare-metal stents were used. Multivessel percutaneous coronary intervention was performed in 30.7% of patients. At follow-up, all patients who successfully responded to the desensitization procedure tolerated aspirin well, without developing allergic reactions. Aspirin was withdrawn in only 1 patient, because of a peptic ulcer. In conclusion, rapid desensitization is safe and highly effective in patients with aspirin sensitivity and coronary artery disease who undergo coronary stent implantation, including those who receive drug-eluting stents.