We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children. Parasitologic and nutritional assessments were carried out at baseline, 6 mo, and 12 mo in 4 nonprogram schools (n = 1002), 4 schools in which students received twice-yearly deworming (n = 952), and 4 schools in which students received thrice-yearly deworming (n = 970) with 500 mg generic mebendazole. Schools were randomly selected for evaluation and allocated to program groups. Relative to no treatment, thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations. The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups, respectively (P < 0.001). The average changes in ferritin concentration were 2.8 and 4.5 microg/L, respectively (P = 0.07). Deworming had no effect on annual hemoglobin change or prevalence of anemia. However, the relative risk of severe anemia (hemoglobin < 70 g/L) was 0.77 (95% confidence limits: 0.39, 1.51) in the twice-yearly deworming group and 0.45 (0.19, 1.08) in the thrice-yearly deworming group. The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia (hemoglobin < 90 g/L) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline. We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic, deworming programs can improve iron status and prevent moderate and severe anemia, but deworming may be needed at least twice yearly.