Limited data are available for sex-related long-term outcomes of patients treated for coronary drug-eluting stent (DES) restenosis. The aim of this observational, retrospective analysis was to close this lack of evidence. Between January 2007 and February 2021, a total of 3511 patients with 5497 in-stent restenosis (ISR) lesions were treated at two large-volume centers in Munich, Germany, of which 763 (21.7%) were female. Endpoints of interest were all-cause mortality and rates of repeat revascularization. Outcomes are presented as Kaplan-Meier event rates. Univariate and multivariate analyses were performed. Female patients were older (72.1 ± 10.4 versus 68.4 ± 10.4 years, p <
0.001) and suffered more often from diabetes (38.8% versus 34.4%, p = 0.029). There was no statistical difference regarding the clinical presentation and interventional treatment strategy. After 10 years, the risk of all-cause mortality was higher in female patients [hazard ratio (HR) 1.18 (1.02-1.35)
p = 0.022]
however, after adjustment for age, the risk did not differ significantly between both sexes [adjusted HR 0.96 (0.83-1.11)
p = 0.6]. Regarding target vessel revascularization (TVR) and non-target vessel revascularization (NTVR), the risk was lower in female patients [HR 0.73 (0.61-0.87)
p <
0.001 and HR 0.74 (0.64-0.86)
p <
0.001] even after age adjustment. No statistical differences were found regarding the risk of target lesion revascularization, target vessel myocardial infarction and stent thrombosis. In the long term, all-cause mortality after percutaneous coronary intervention of DES-ISR did not differ between both sexes after age adjustment. The risk of TVR and NTVR was lower in female patients even after age adjustment.