INTRODUCTION: Malaria infection in pregnancy (MIP) remains a public health problem in the tropical and subtropical regions of the world with ninety percent of the global malaria burden occurring in Sub-Saharan Africa. The risks of malaria infection are greatest in primigravidae and decrease with increasing parity; with multi-parous women being less affected. In order to reduce the burden of malaria infections, several interventions have been recommended by the World Health Organization for the control of malaria infection. These include, the use of insecticide treated nets (ITN), intermittent preventive treatment for malaria in pregnancy (IPTp) and prompt case management of malaria illness. The benefit of IPTp is however threatened by the emergence of Plasmodium falciparum resistance to known anti-malarial agents for chemoprophylaxis and treatment. OBJECTIVES: The main objective of this study was to compare the efficacy of azithromycin with Sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy (IPTp). METHODOLOGY: This was a prospective comparative study conducted at the University College Hospital, Ibadan over a period of eight months from November 2011 to July 2012, among pregnant women attending antenatal clinic. The participants were randomized into two groupsgroup one participants received sulphadoxine-pyrimethamine while group two participants received azithromycin. A data collection form was completed for each participant; they were followed up and blood samples collected at intervals for evaluation of malaria parasitaemia; maternal peripheral blood film, placental and cord blood samples were also collected at delivery. The data collected was entered, cleaned and computer analysed using SPSS version 16.