Background The World Health Organization (WHO) recommends universal oral iron supplementation for pregnant women at a daily dose of 60mg of elemental iron to prevent anaemia in pregnancy. This regimen has been shown to be sub-optimal by the International Nutritional Anaemia Consultative Group that has recommended an increased twice daily dose in areas where anaemia is prevalent as in Nigeria. The appropriate dose regimen remains a subject of continuing research in various developing countries with tendency toward twice daily dose regimen but, patients’ compliance appears to be a challenge. Whether twice or daily dose schedules proffer a better outcome appears to be poorly researched in Nigeria. Objective The Objective of this study was to compare the effectiveness and efficacy of the once versus the twice daily dose of ferrous sulphate in pregnant women in preventing iron deficiency anaemia in pregnancy and associated complications. Methods One hundred and eighty two (182) pregnant women between the gestational ages of 14-24 weeks with Hb level ≥ 10g/dl but ≤14.5 g/dl were recruited during the antenatal booking clinic and randomized to receive either once daily dose (65mg of elemental iron) or twice daily dose (130mg of elemental iron) of ferrous sulphate after informed consent was obtained. Pre- supplementation haemoglobin, serum iron and ferritin levels were assessed at recruitment. The post –supplementation levels of haemoglobin, serum iron and ferritin were re-assessed at 37 weeks gestation. For those women who delivered earlier, post supplementation levels were assessed in labour. Women were encouraged to attend their scheduled ANC visits and to deliver in our facility. At each visit, side effects if any were recorded. Their blister packets of ferrous sulphate were also checked for compliance. The gestational age at delivery and birth weight were assessed and recorded.