Iron deficiency is the most common and widespread nutritional disorder in the world, affecting millions of people in both nonindustrialized and industrialized countries. We estimated the costs, effects, and cost-effectiveness of iron supplementation and iron fortification interventions in 4 regions of the world. The effects on population health were arrived at by using a population model designed to estimate the lifelong impact of iron supplementation or iron fortification on individuals benefiting from such interventions. The population model took into consideration effectiveness, patient adherence, and geographic coverage. Costs were based on primary data collection and on a review of the literature. At 95% geographic coverage, iron supplementation has a larger impact on population health than iron fortification. Iron supplementation would avert <12,500 disability adjusted life years (DALY) annually in the European subregion, with very low rates of adult and child mortality, to almost 2.5 million DALYs in the African and Southeast Asian subregions, with high rates of adult and child mortality. On the other hand, fortification is less costly than supplementation and appears to be more cost effective than iron supplementation, regardless of the geographic coverage of fortification. We conclude that iron fortification is economically more attractive than iron supplementation. However, spending the extra resources to implement iron supplementation is still a cost-effective option. The results should be interpreted with caution, because evidence of intervention effectiveness predominantly relates to small-scale efficacy trials, which may not reflect the actual effect under expected conditions.