Background: The future burden of non-communicable diseases (NCDs) depends on numerous factors such as population ageing, evolution of societal trends, behavioural and physiological risk factors of individuals (e.g. smoking, alcohol use, obesity, physical inactivity, and hypertension). This study aims to assess the burden of NCDs in Europe by 2050 under alternative scenarios. Methods: This study combines qualitative and quantitative forecasting techniques to examine how population health in Europe may evolve from 2015 to 2050, taking into account future societal trends. Four scenarios were developed (one business-as-usual scenario, two response scenarios and one pessimistic scenario) and assessed against 'best' and 'worst'-case scenarios. This study provides quantitative estimates of both diseases and mortality outcomes, using a microsimulation model incorporating international survey data. Findings: Each scenario is associated with a different risk factor prevalence rate across Europe during the period 2015-2050. The prevalence and incidence of NCDs consistently increase during the analysed time period, mainly driven by population ageing. In more optimistic scenarios, diseases will appear in later ages, while in the pessimistic scenarios, NCDs will impair working-age people. Life expectancy is expected to grow in all scenarios, but with differences by up to 4 years across scenarios and population groups. Premature mortality from NCDs will be reduced in more optimistic scenarios but stagnate in the worst-case scenario. Interpretation: Population ageing will have a greater impact on the spread of NCDs by 2050 compared to risk factors. Nevertheless, risk factors, which are influenced by living environments, are an important factor for determining future life expectancy in Europe.