Background and Aims: Previous evaluations of smoking cessation interventions in pregnancy have several limitations. Our solution to these limitations is the Economics of Smoking in Pregnancy (ESIP) model, which estimates the life-time cost-effectiveness of smoking cessation interventions in pregnancy from a National Health Service (NHS) and personal social services perspective. We aim to (1) describe how ESIP has been constructed and (2) illustrate its use with trial data. Methods: ESIP links mothers’ and offspring pregnancy outcomes to estimate the burdens of smoking-related disease they experience with different rates of smoking in pregnancy, both in pregnancy and throughout their life-times. Smoking rates are inputted by model users. ESIP then estimates the costs of treating disease burdens and also mothers’ and offspring life-years and quality-adjusted life years (QALYs). By comparing costs incurred and healthy life following different smoking rates, ESIP estimates incremental cost-effectiveness and benefit–cost ratios for mothers or offspring or both combined. We illustrate ESIP use using data from a pragmatic randomized controlled trial that tested a smoking cessation intervention in pregnancy. Results: Throughout women's and offspring life-times, the intervention proved cheaper than usual care, having a negative incremental cost of £38.37 (interquartile range = £21.46–56.96) and it improved health, demonstrating a 0.04 increase in incremental QALYs for mothers and offspring, implying that it is ‘dominant’ over usual care. Benefit–cost ratios suggested that every £1 spent would generate a median of £14 (interquartile range = £8–20) in health-care savings. Conclusions: Economics of Smoking in Pregnancy is the first economic model to link mothers’ and infants’ costs and benefits while reporting cost-effectiveness in readily-comparable units. Using ESIP with data from a trial which reported only short-term economic analysis showed that the intervention was very likely to be cost-effective in the longer term and to generate health-care savings.