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Data regarding the duration of dual antiplatelet therapy (DAPT) in patients with drug-eluting stent restenosis (DES-ISR) treated with percutaneous coronary intervention (PCI) and drug-eluting balloons (DEB) or DES are not unambiguous.To evaluate the relationship between long-term outcomes and the length of DAPT in patients treated with PCI due to DES-ISR with DEB or DES.Overall, a total of 1,367 consecutive patients with DES-ISR, who underwent PCI with DEB or DES between 2008 and 2019 entered the study. The mean length of the follow-up was 1,298.7 ±794 days. We assessed study endpoints according to the duration of DAPT (≤ 3 vs.3 and ≤ 6 vs.6 months) before and after propensity score matching (PSM): stroke, target lesion revascularisation (TLR), target vessel revascularisation (TVR), myocardial infarction (MI), death and device oriented composite endpoints (DOCE). Kaplan-Meier estimates were created to differentiate long-term outcomes.Pairwise contrast analysis considering type of PCI (DES vs. DEB) and duration of DAPT (≤ 6 vs.6 months) before PSM revealed superiority of DES + DAPT6 months vs. DEB + DAPT6 months for DOCE (Treatment with DAPT in patients with DES-ISR is related to better long-term outcomes in the case of PCI with DES than DEB. DAPT6 months is related to the greater rate of strokes, independently of the type of treatment (DES and DEB) than DAPT ≤ 6 months.