The experimental oral antiplatelet agent AZD6140 causes dyspnea in randomized trials. Whether clopidogrel may also cause dyspnea remains controversial. We sought to define the incidence and causes of dyspnea in a large post-percutaneous coronary intervention (PCI) cohort based on open-labeled consecutive registry analysis of in-hospital charts and discharge diagnoses. Data were collected at six-month follow-up by means of telephone interviews or returned questionnaires during outpatient visits. Patients undergoing coronary stent implantation were loaded with 600 mg clopidogrel followed by 75 mg/daily in combination with 75-325 mg of aspirin daily for at least six months. Data from 3,719 patients were analyzed. Dyspnea was diagnosed in 157 (4.2%) patients caused by chronic obstructive pulmonary disease (n = 43 or 27% of the dyspnea group), heart failure (n = 30 or 19%), cancer (n = 22 or 14%), pneumonia (n = 17 or 11%); asthma (n = 8 or 5%), pulmonary hypertension (n = 8 or 5%); pericarditis (n = 5 or 3%); cardiac arrhythmias (n = 4 or 2.5%); pleural effusion (n = 1), pulmonary embolism (n = 1), anxiety (n = 1), or unknown (n = 17, or 11%). The incidence of dyspnea at six months in a post-stent cohort treated with aspirin and clopidogrel is low (4.2%). The majority of patients with dyspnea (140/157) exhibit a distinct underlying disease or condition, in contrast to only 17 patients (0.45% of total cohort) in whom the pathogenesis of dyspnea remained unidentified. These data closely match the frequency of dyspnea that was observed in the CAPRIE trial, suggesting that therapy with clopidogrel, and/or aspirin holds very small (if any) risk for dyspnea.