To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia.