Pregnant women are vulnerable to malaria, with significant implications both for their health and for the pregnancy. Sulfadoxine-pyrimethamine (SP) is currently the first line drug for the treatment of malaria in pregnancy in Tanzania and surrounding countries, but resistance is emerging rapidly. Alternative drugs must be found, and new drugs and drug combinations are being recommended by many for deployment as first line treatment at the point that SP resistance forces a policy change. However, there are few data on the safety and efficacy of these combinations in pregnant women. This randomised trial aims to assess efficacy and safety, including birth outcome, in pregnant women with malaria in the second or third trimesters. A total of 900 pregnant women will be randomised either to standard treatment (SP) or to one of three potential drugs, or drug combinations recently recommended by a WHO expert panel. These will be SP-amodiaquine, chlorproguanil-dapsone (Lapdap), and amodiaquine-artesunate. Primary outcome will be treatment failure. Secondary outcomes will include 28 day slide clearance, maternal side effects, foetal viability and birth outcome.