Iron deficiency and iron deficiency anemia (IDA) are major public health problems worldwide, especially in young women. Oral iron supplementation can be an effective strategy to treat and prevent IDA, but guidelines vary. Some experts recommend doses of 150-200 mg elemental iron per day, with the dose split through the day. However, recent studies suggest this may not be an optimal regimen. The fraction of iron absorbed from high doses of oral iron is low, and unabsorbed iron can cause gut irritation, inflammation and dysbiosis, and these reduce compliance. In recent studies using serum hepcidin profiles and stable iron isotopes to quantify iron absorption in young women, we have shown that: (a) oral iron doses ≥60 mg in iron-deficient women, and doses ≥100 mg in women with IDA, stimulate an acute increase in hepcidin that persists 24 h after the dose, but subsides by 48 h; (b) therefore, to maximize fractional iron absorption, oral doses ≥60 mg should be given on alternate days; (c) the circadian increase in plasma hepcidin is augmented by a morning iron dose; therefore, iron doses should not be given in the afternoon or evening after a morning dose. If rate of Hb response is important, a pooled analysis of our data done for this review indicates that total iron absorption is also higher if twice the target daily iron dose is given on alternate days. In summary, these studies suggest changing from daily to alternate-day schedules and from divided to morning single doses increases iron absorption and may reduce side effects. Thus, providing morning doses of 60-120 mg iron as a ferrous salt given with ascorbic acid on alternate days may be an optimal oral dosing regimen for women with iron-deficiency and mild IDA.