BACKGROUND: Adjuvant clopidogrel therapy is essential after drug-eluting stent (DES) implantation. The frequency with which patients delay filling a clopidogrel prescription after DES implantation and the association of this delay with adverse outcomes is unknown. METHODS AND RESULTS: This was a retrospective cohort study of patients discharged after DES implantation from 3 large integrated health care systems. Filling a clopidogrel prescription was based on pharmacy dispensing data. The primary end point was all-cause mortality or myocardial infarction (MI). Of 7402 patients discharged after DES implantation, 16% (n=1210) did not fill a clopidogrel prescription on day of discharge and the median time delay was 3 days (interquartile range, 1 to 23 days). Compared with patients filling clopidogrel on day of discharge, patients with any delay in filling clopidogrel had higher death/MI rates during follow-up (14.2% versus 7.9%; P<0.001). In multivariable analysis, patients with any delay had increased risk of death/MI (hazard ratio, 1.53; 95% confidence interval, 1.25 to 1.87). Patients with any delay remained at increased risk of adverse outcomes when the delay cutoff was changed to >1, >3, or >5 days after discharge. Factors associated with delay included older age, prior MI, diabetes, renal failure, prior revascularization, cardiogenic shock, in-hospital bleeding, and clopidogrel use within 24 hours of admission. CONCLUSIONS: One in 6 patients delay filling their index clopidogrel prescription after hospital discharge after DES implantation. This delay was associated with increased risk of adverse outcomes and highlights the importance of the transition period from hospital discharge to outpatient setting as a potential opportunity to improve care delivery and patient outcomes.