Solomon Islands is a malarious nation in the Pacific with all four human Plasmodium species present. Although chloroquine prophylaxis is recommended for pregnant women, itseffectiveness is uncertain because of chloroquine resistance. A parallel-group, open label, individually randomised superiority trial comparing weekly chloroquine prophylaxis (CQ) with intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) was conducted among pregnant women aged 15 to 49 years between August 2009- June 2010. The study shows that the use of SP for IPTp is not suitable for prevention of malaria in pregnancy in Solomon Islands, given the low malaria prevalence and the possible high prevalence of sulfa-allergy. Scaling up of transmission-reducing interventions has probably contributed to the malaria reduction in Honiara.