Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P=0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P=0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P=0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P=0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.