AbstractNon-pharmaceutical interventions (NPIs) and vaccination are two fundamental approaches for mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, the real-world impact of NPIs versus vaccination, or a combination of both, on COVID-19 remains uncertain. To address this, we built a Bayesian inference model to assess the changing effect of NPIs and vaccination on reducing COVID-19 transmission, based on a large-scale dataset including epidemiological parameters, virus variants, vaccines, and climate factors in Europe from August 2020 to October 2021. We found that (1) the combined effect of NPIs and vaccination resulted in a 53% (95% confidence interval: 42–62%) reduction in reproduction number by October 2021, whereas NPIs and vaccination reduced the transmission by 35% and 38%, respectively; (2) compared with vaccination, the change of NPI effect was less sensitive to emerging variants; (3) the relative effect of NPIs declined 12% from May 2021 due to a lower stringency and the introduction of vaccination strategies. Our results demonstrate that NPIs were complementary to vaccination in an effort to reduce COVID-19 transmission, and the relaxation of NPIs might depend on vaccination rates, control targets, and vaccine effectiveness concerning extant and emerging variants.