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Background: Early studies evaluating the performance of bioresorbable scaffold (BRS) Absorb in in-stent restenosis (ISR) lesions indicated promising short-term to mid-term outcomes., Aims: To evaluate long-term outcomes (up to 5 years) of patients with ISR treated with the Absorb BRS., Methods: We did an observational analysis of long-term outcomes of patients treated for ISR using the Absorb BRS (Abbott Vascular, Santa Clara, California, USA) between 2013 and 2016 at the Heart Centre Luzern. The main outcomes included a device-oriented composite endpoint (DOCE), defined as composite of cardiac death, target vessel (TV) myocardial infarction and TV revascularisation, target lesion revascularisation and scaffold thrombosis (ScT)., Results: Overall, 118 ISR lesions were treated using totally 131 BRS among 89 patients and 31 (35%) presented with an acute coronary syndrome. The median follow-up time was 66.3 (IQR 52.3-77) months. A DOCE had occurred in 17% at 1 year, 27% at 2 years and 40% at 5 years of all patients treated for ISR using Absorb. ScTs were observed in six (8.4%) of the cohort at 5 years., Conclusions: Treatment of ISR using the everolimus-eluting BRS Absorb resulted in high rates of DOCE at 5 years. Interestingly, while event rates were low in the first year, there was a massive increase of DOCE between 1 and 5 years after scaffold implantation. With respect to its complexity, involving also a more unpredictable vascular healing process, current and future BRS should be used very restrictively for the treatment of ISR., Competing Interests: Competing interests: MM, GMC, AA-T, MW, FM, TS, LV, ST and RK report no conflicts of interest. MB has received consulting and speaker fees from Amgen, Astra Zeneca, Bayer and Mundipharma. FC has received consulting and speaker fees from SIS Medical and Abbott Vascular., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)