Background: Nutritional iron deficiency anemia is of a major concern in Egypt, especially during pregnancy. The most commonly used treatment is oral iron mainly as ferrous sulfate. Unfortunately, ferrous sulfate has low efficacy with many adverse effects. Lactoferrin is a glycoprotein which belongs to proteins which have the ability to bind and transfer iron. This study was done to assess the compliance, efficacy and safety of lactoferrin in comparison to ferrous sulfate. Methods: This randomized clinical trial was conducted in outpatient clinic under supervision of Department of Obstetrics and Gynecology, Faculty of medicine, Ain Shams University, Cairo, Egypt from August 2019 to February 2020. 140 women with iron deficiency anemia in second trimester were recruited and randomly assigned to either group. First group received lactoferrin 200 mg sachets once daily and second group received 100 mg of dried ferrous sulfate capsules twice daily for 4 consecutive weeks. Compliance to treatment, efficacy and side effects were recorded.  Results: Compliance is better in lactoferrin group in comparison to ferrous sulfate group. Maternal side effects were significantly less common in lactoferrin group than in ferrous sulfate group. The increase in hemoglobin was significantly higher in lactoferrin group. Number of cases achieved Hb level ≥10.5 was more frequent in lactoferrin group. Conclusion: Oral lactoferrin is more tolerated and effective as compared to traditional treatment by ferrous sulfate.