We use analogues of atmospheric patterns to investigate changes in the three most devastating Acqua Alta (flooding) events in the lagoon of Venice associated with intense Mediterranean cyclones occurred in 1966, 2018 and 2019. Our results provide evidence that changes in atmospheric circulation, although not necessarily anthropogenically driven only, are linked to the severity of these events. We also evaluate the cost and benefit of the MoSE system, which was designed to protect against flooding. Our analysis shows that the MoSE has already provided protection against analogues of the most extreme events, which occurred in 1966, while for 2018 and 2019 events our analysis is non-conclusive because of the lack of analogues situations of those events. These findings have significant implications for the future of Venice and other coastal cities facing similar challenges from rising sea levels due to extreme events. This study also provide a pathway to evaluate the effectiveness of adaptation in a scenario more frequent and intense extreme events if higher global warming levels will be reached.