Efforts to mitigate the devastation of tobacco-attributable morbidity and mortality in the European Union (EU) are founded on its newly adopted Tobacco Products Directive (TPD) along with the first-ever health treaty, the WHO Framework Convention on Tobacco Control (FCTC). The aim of this Horizon 2020 Project entitled European Regulatory Science on Tobacco: Policy Implementation to Reduce Lung Disease (EURESTPLUS) is to monitor and evaluate the impact of the implementation of the TPD across the EU, within the context of WHO FCTC ratification. To address this aim, EUREST-PLUS consists of four objectives: 1) To create a cohort study of 6000 adult smokers in six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) within a pre-TID vs post-TPD implementation study design; 2) To conduct secondary dataset analyses of the Special Eurobarometer on Tobacco Survey (SETS); 3) To document changes in e-cigarette product parameters (technical design, labelling/packaging and chemical composition) pre-TID vs post-TPD; and 4) To enhance innovative joint research collaborations on chronic non-communicable diseases. Through this methodological approach, EUREST-PLUS is designed to generate strong inferences about the effectiveness of tobacco control policies, as well as to elucidate the mechanisms and factors by which policy implementation translates to population impact. Findings from EUREST-PLUS have potential global implications for the implementation of innovative tobacco control policies and its impact on the prevention of lung diseases.