Burden of Disease studies-such as the Global Burden of Disease (GBD) Study-quantify health loss in disability-adjusted life-years. However, these studies stop short of quantifying the future impact of interventions that shift risk factor distributions, allowing for trends and time lags. This methodology paper explains how proportional multistate lifetable (PMSLT) modelling quantifies intervention impacts, using comparisons between three tobacco control case studies [eradication of tobacco, tobacco-free generation i.e. the age at which tobacco can be legally purchased is lifted by 1 year of age for each calendar year) and tobacco tax]. We also illustrate the importance of epidemiological specification of business-as-usual in the comparator arm that the intervention acts on, by demonstrating variations in simulated health gains when incorrectly: (i) assuming no decreasing trend in tobacco prevalence; and (ii) not including time lags from quitting tobacco to changing disease incidence. In conjunction with increasing availability of baseline and forecast demographic and epidemiological data, PMSLT modelling is well suited to future multiple country comparisons to better inform national, regional and global prioritization of preventive interventions. To facilitate use of PMSLT, we introduce a Python-based modelling framework and associated tools that facilitate the construction, calibration and analysis of PMSLT models.© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.