Funder: European and Developing Countries Clinical Trials Partnership (EDCTP); doi: https://doi.org/10.13039/501100001713 / Funder: MRC Centre for Global Infectious Disease Analysis (MR/R015600/1), jointly funded by the U.K. Medical Research Council (MRC) and the U.K. Foreign, Commonwealth and Development Office (FCDO), under the MRC/FCDO Concordat agreement. Community Jameel. The UK Research and Innovation (MR/V038109/1), the Academy of Medical Sciences Springboard Award (SBF004/1080), The MRC (MR/R015600/1), The BMGF (OPP1197730), Imperial College Healthcare NHS Trust- BRC Funding (RDA02), The Novo Nordisk Young Investigator Award (NNF20OC0059309) and The NIHR Health Protection Research Unit in Modelling Methodology. S. Bhatt thanks Microsoft AI for Health and Amazon AWS for computational credits. / Funder: EA Funds / Funder: University of Oxford (Oxford University); doi: https://doi.org/10.13039/501100000769 / Funder: DeepMind / Funder: OpenPhilanthropy / Funder: UKRI Centre for Doctoral Training in Interactive Artificial Intelligence (EP/S022937/1) / Funder: Augustinus Fonden (Augustinus Foundation); doi: https://doi.org/10.13039/501100004954 / Funder: Knud Højgaards Fond (Knud Højgaard Fund); doi: https://doi.org/10.13039/501100009938 / Funder: Kai Lange og Gunhild Kai Langes Fond (Kai Lange and Gunhild Kai Lange Foundation); doi: https://doi.org/10.13039/501100008206 / Funder: Aage og Johanne Louis-Hansens Fond (Aage and Johanne Louis-Hansen Foundation); doi: https://doi.org/10.13039/501100010344 / Funder: William Demant Foundation / Funder: Boehringer Ingelheim Fonds (Stiftung für medizinische Grundlagenforschung); doi: https://doi.org/10.13039/501100001645 / Funder: Imperial College COVID-19 Research Fund / Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289 / Abstract: European governments use non-pharmaceutical interventions (NPIs) to control resurging waves of COVID-19. However, they only have outdated estimates for how effective individual NPIs were in the first wave. We estimate the effectiveness of 17 NPIs in Europe’s second wave from subnational case and death data by introducing a flexible hierarchical Bayesian transmission model and collecting the largest dataset of NPI implementation dates across Europe. Business closures, educational institution closures, and gathering bans reduced transmission, but reduced it less than they did in the first wave. This difference is likely due to organisational safety measures and individual protective behaviours—such as distancing—which made various areas of public life safer and thereby reduced the effect of closing them. Specifically, we find smaller effects for closing educational institutions, suggesting that stringent safety measures made schools safer compared to the first wave. Second-wave estimates outperform previous estimates at predicting transmission in Europe’s third wave.