BACKGROUND: In sub-Saharan Africa, malaria continues to cause over 10,000 maternal deaths and 75,000 to 200,000 infant deaths. Successful control of malaria in pregnancy could save lives of mothers and babies and is an essential part of antenatal care in endemic areas. The primary objective is to determine the protective efficacy of community-scheduled screening and treatment (CSST) using community health workers (CHW) against the primary outcome of prevalence of placental malaria. The secondary objectives are to determine the protective efficacy of CSST on maternal anaemia, maternal peripheral infection, low birth weight, selection of sulfadoxine-pyrimethamine (SP) resistance markers, and on antenatal clinic (ANC) attendance and coverage of intermittent preventive treatment during pregnancy (IPTp-SP). METHODS/DESIGN: This is a multi-centre cluster-randomised controlled trial involving three countries with varying malaria endemicity; low (The Gambia) versus high transmission (Burkina Faso and Benin), and varying degrees of SP resistance (high in Benin and moderate in Gambia and Burkina Faso). CHW and their related catchment population who are randomised into the intervention arm will receive specific training on community-based case management of malaria in pregnancy. All women in both study arms will be enrolled at their first ANC visits in their second trimester where they will receive their first dose of IPTp-SP. Thereafter, CHW in the intervention arm will perform scheduled monthly screening and treatment in the womens homes. At time of delivery, a placental biopsy will be collected from all women to determine placental malaria. At each contact point, filter paper and blood slides will be collected for detection of malaria infection and SP resistance markers. DISCUSSION: To reach successful global malaria control, there is an urgent need to access those at greatest risk of malaria infection. The project is designed to develop a low-cost intervention in pregnant women which will have an immediate impact on the malaria burden in resource-limited countries. This will be done by adding to the standard IPTp-SP delivered through the health facilities: an "extension" strategy to the communities in rural areas thus bringing health services closer to where women live. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN37259296 (5 July 2013), and clinicaltrials.gov: NCT01941264 (10 September 2013).