Background: In-stent restenosis (ISR) is when the inner diameter gets much smaller in the area that has a stent in it after a successful percutaneous coronary intervention (PCI). Aim: To assess the safety and efficacy of a drug-eluting balloon (DEB) with paclitaxel (PEB) as compared with the implantation of a 2nd-generation drug-eluting stent (DES) for the treatment of ISR. Patients and methods: This research included 60 patients admitted to King Abdullah Medical Complex Hospital in Jeddah who presented with angina or objective evidence of ischemia & revealed ISR on angiography (fifty percent stenosis on visual evaluation) in the period from 2018 to 2021. Individuals were separated into 2 groups: Group I, which involved thirty cases managed by DES, & Group II, which involved thirty cases managed by DEB