Iron polymaltose complex (IPC) offers similar efficacy with superior tolerability to ferrous sulfate in adults, but randomized trials in children are rare. In a prospective, open-label, 4-month study, 103 children aged >6 months with iron deficiency anemia (IDA) were randomized to IPC once daily or ferrous sulfate twice daily, (both 5 mg iron/kg/day). Mean increases in Hb to months 1 and 4 with IPC were 1.2 ± 0.9 g/dL and 2.3 ± 1.3 g/dL, respectively, (both P = 0.001 versus baseline) and 1.8 ± 1.7 g/dL and 3.0 ± 2.3 g/dL with ferrous sulfate (both P = 0.001 versus baseline) (n.s. between groups). Gastrointestinal adverse events occurred in 26.9% and 50.9% of IPC and ferrous sulfate patients, respectively (P = 0.012). Mean acceptability score at month 4 was superior with IPC versus ferrous sulfate (1.63 ± 0.56 versus 2.14 ± 0.75, P = 0.001). Efficacy was comparable with IPC and ferrous sulfate over a four-month period in children with IDA, but IPC was associated with fewer gastrointestinal adverse events and better treatment acceptability.