Background Coeliac disease is frequently diagnosed after a long delay resulting in increased morbidity and mortality. Aims To define the parameters which have the highest impact on the cost-effectiveness of mass screening for coeliac disease. Methods A Markov model examined a coeliac disease screening programme of the healthy young-adult general population compared with a no-screening strategy. The main outcome measures were quality adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Effects of variables were examined using sensitivity analyses. Results The screening strategy resulted in a gain of 0.0027 QALYs. The ICER of screening vs. no-screening strategy was US$48 960/QALYs. The variables with the largest impact on cost effectiveness were: the time delay from symptom onset to diagnosis, the utility of adherence to a gluten-free diet (GFD) and the prevalence of coeliac disease. Screening would be cost-effective if the time delay to diagnosis is longer than 6 years and utility of GFD adherence is greater than 0.978. Conclusions Our model suggests that mass screening for coeliac disease of the young-adult general population is associated with improved QALYs and is a cost effectiveness strategy. Shortening of the time-delay to diagnosis by heightened awareness of health-care professionals may be a valid alternative to screening.