Iron deficiency anemia (IDA) is still a major nutritional and public health problem in developing countries. The prevalence among young children and pregnant women is particularly high. Daily oral supplementation with medicinal iron is considered an effective strategy for reducing the incidence of IDA but non-compliance is a major problem with this strategy. We undertook this study to compare the results of once-weekly vs. daily oral iron supplementation in schoolchildren. Sixty children ranging between 5 and 10 years with iron deficiency anemia were selected from a school in Karachi, Pakistan and were divided into two equal groups, i.e., daily and weekly supplementation groups. Hemoglobin (Hb), hematocrit (Hct), serum iron, total iron binding capacity (TIBC), and serum ferritin were determined before the start of the study. Ferrous sulfate (200 mg) was given daily to the daily supplementation group and once-weekly to the weekly supplementation group for 2 months. When post-supplementation values of the above-mentioned parameters were determined, a significant improvement was observed in all parameters in both groups. It is concluded that once-weekly iron supplementation is as effective as daily supplementation for the treatment of iron deficiency anemia. Moreover, weekly iron supplementation is cost effective and has no or fewer side-effects.