Abstract Background Biodegradable polymer (BP) drug-eluting stents (DES) have shown similar safety and efficacy compared with second-generation durable polymer (DP)-DES in several randomized trials and meta-analyses. However, study participants were generally maintained on a standard dual antiplatelet therapy (DAPT) for at least 6 months after percutaneous coronary intervention (PCI). Therefore, the differences in thrombogenicity between these two stent technologies may have been unappreciated, especially among patients with acute coronary syndrome (ACS). Purpose We aimed to compare the safety and efficacy of BP Biolimus-Eluting Stent (BP-BES) versus 2nd generation DP-DES among ACS patients undergoing PCI and receiving ticagrelor alone or in combination with aspirin. Methods We pooled individual patient-level data from two randomized controlled trials, the Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT, n=9,006) (1) and the GLOBAL LEADERS Adjudication Sub-Study (GLASSY, n=7,585) (2). In order to reduce biases related to trial design differences, only NST-ACS patients not fulfilling any exclusion criterion of both studies were included and 2 separate analysis for short (0 to 3 months after PCI) and long-term (3 to 12 months after PCI) outcomes were performed. Patients were stratified according to the stent used at index PCI (BP-BES vs 2nd generation DP-DES). In both analysis, the primary outcome was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction and definite or probable stent thrombosis); the key secondary outcomes were target-vessel failure (TVF) and BARC 2, 3 or 5 bleeding. Events rate and risk were assessed separately for the two study periods and subsequently 12-months risk estimates were derived by pooling the results of the two analysis. Results Out of 7,729 and 6,572 NST-ACS patients included in the two analysis, 2,321 (30%) and 2,211 (33.6%) received a BP-BES, respectively. Among patients treated with BP-BES versus DP-DES, the occurrence of MACE was similar at 3 months after PCI (1.1% vs 1.4%, adjusted HR 0.81, 95% CI 0.51–1.29), while it was significantly lower in the former group between 3 and 12 months (1.7% vs 3.1%, adj. HR 0.46, 95% CI 0.32–0.67) and in the overall period (pooled adjusted HR estimate 0.58, 95% CI 0.43–0.77). Similarly, significant differences were observed for TVF and BARC 2, 3, or 5 bleeding, whose risk at 12 months was lower among BP-BES than DP-DES patients (pooled adj. HR estimate 0.49, 95% CI 0.38–0.63 and 0.79, 95% CI 0.79, 95% CI 0.65–0.97, respectively). Conclusion As compared to 2nd generation DP-DES, BP-BES was associated with a lower risk of MACE, TVF and bleeding among NST-ACS patients undergoing PCI and treated with ticagrelor with or without aspirin. The findings of this analysis are exploratory and need further confirmation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Biosensors (Singapore)