BACKGROUND: Malaria, especially in tropical Africa, is one of the leading causes of maternal and perinatal morbidity and mortality. Various drugs have been used in the past for malaria prophylaxis in pregnancy without much success. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) has been proven efficacious in reducing the burden of malaria in pregnancy. There is need to compare its effectiveness with that of proguanil in order to have a possible alternative drug to be used in our environment. OBJECTIVE: To compare the effectiveness of sulphadoxine – pyrimethamine and proguanil as malaria chemoprophylaxis in pregnancy. METHODOLOGY: Pregnant women attending antenatal clinic at the University of Port Harcourt Teaching Hospital were randomly selected at booking and monitored till delivery. Blood samples were taken to confirm the presence of malaria parasites as well as anaemia. Intermittent preventive treatment for malaria using sulphadoxine (500mg) and pyrimethamine (25mg) combination was given to one group of participants while the other group received daily proguanil (100mg) as prophylaxis. Mothers were screened at delivery to determine the presence or absence of malaria parasitaemia and anaemia.