<p>Chronic kidney disease (CKD) is associated with increased platelet reactivity following stent implantation. However, the effect of sex on platelet reactivity remains unclear and requires further investigation. We evaluated the impact of high platelet reactivity (HPR) and sex on 5-year outcomes in patients with CKD undergoing percutaneous coronary intervention (PCI) using drug-eluting stents (DES). From the Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent–Treated Patients With Coronary Artery Disease Consortium, 2126 patients with CKD were included. Patients were categorized into HPR (<i>n</i> = 939) and non-HPR (<i>n</i> = 1187) groups based on P2Y₁₂ reaction unit values and further subdivided by sex. The primary endpoint was the 5-year incidence of patient-oriented composite outcomes (POCO), comprising all-cause mortality, myocardial infarction, stent thrombosis, or stroke. The secondary outcomes included individual POCO components and major bleeding events. In the HPR group, no significant sex differences were observed in 5-year outcomes. However, in the non-HPR group, female patients had significantly lower rates of POCO (adjusted hazard ratio [aHR]: 0.552; <i>P</i> = 0.002) and all-cause mortality (aHR: 0.373; <i>P</i> &lt; 0.001) than male patients. No significant differences in outcomes were observed between the HPR and non-HPR groups for either sex. The incidence of major bleeding did not differ by sex in either HPR (<i>P</i> = 0.586) or non-HPR group (<i>P</i> = 0.325). In patients with CKD undergoing PCI with DES, long-term outcomes did not differ by sex in the HPR group, whereas female patients in the non-HPR group had better survival than male patients.</p> Graphical abstract <p></p>