Biofortification is a strategy for overcoming human zinc (Zn) deficiency, especially in rural areas of developing countries. Actually, biofortification by foliar Zn application has been demonstrated at small scale, but not at large scale due to the absence of economic analysis. Therefore, here, we conducted the first cost-effectiveness analysis using the method of "disability-adjusted life year" measuring the health burden. We thus quantified the cost of agronomic biofortification of wheat with Zn in three major wheat-growing regions of China. Our results show that the current annual health burden due to human Zn deficiency, defined as numbers of disabilityadjusted life years lost, is 0.21 million years for the region under single wheat plantation, 0.79 million years for the region under wheat-maize rotation, and 0.38 million years for the region under wheat-rice rotation. Comparing with traditional wheat diets in these three regions, the consumption of agronomically Zn-biofortified wheat diets could increase the daily Zn intakes of infants and children under 5 years of age. These increased daily Zn intakes consequently reduce the health burden due to human Zn deficiency in these regions by up to 56.6 %.