Background Malaria in pregnancy is an important cause of foetal and maternal morbidity and mortality. Sulphadoxine-pyrimethamine (SP) intermittent preventive treatment (IPT) have been used in many centres in the prevention of malaria in pregnancy. But there has been increasing reports of resistance to SP across the globe. Hence, assessment of its efficacy is important in malaria endemic areas like Nigeria. Objective To compare the efficacy of sulphadoxine – pyrimethamine intermittent preventive treatment and Proguanil chemoprophylaxis in the prevention of malaria in pregnancy at Aminu Kano Teaching Hospital Kano. Study design, settings and subjects This was a comparative study, conducted at Aminu Kano Teaching Hospital, which involved only primigravidas , attending antenatal clinic of Aminu Kano Teaching Hospital. Methods Participants were divided into two study groups; the sulphadoxine –pyrimethamine group (experimental group) and the proguanil group (controls) by block randomization. At recruitment, blood was taken for packed cell volume (PCV), and those with PCV of < 24% were excluded. All recruited clients were treated with Artemisinine combination therapy (ACT) using artemether and lumefantrine combination, to clear initial parasitaemia, before SP and proguanil hydrochloride tablets were given to their respective groups. At 34 weeks maternal blood was checked for PCV, and peripheral malaria parasitaemia in the two groups. The data obtained was recorded using tables. Statistical analysis was done using computer software SPSS Version 11.0, Ilinois, USA. Students’t-test, Z-test and chi-square were used to compare means and proportions respectively for statistically significant differences, setting the level of significance (P-value) at P< 0.05.