Pregnant women and their unborn children are vulnerable to malaria increasing the risk of maternal anaemia, low birth weight (LBW) and intrauterine growth retardation. There is little evidence on the cost-effectiveness of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated bed nets (ITNs) in areas of low transmission. A randomised controlled trial with three arms was conducted in antenatal clinics in Kabale District, Uganda, an epidemic-prone highland area of low malaria transmission. The interventions were (i) IPTp with sulphadoxine/pyrimethamine (SP) given twice during pregnancy (IPTp-SP); (ii) ITNs alone; and (iii) a combined intervention with both ITNs and IPTp-SP. Primary health outcomes were LBW and maternal anaemia. The costs of providing IPTp-SP and ITNs as well as treatment of malaria episodes were captured from all health centres in the study area. There were no significant differences in health outcomes among the three interventions. The cost-effectiveness analysis and sensitivity analyses performed did not provide convincing support for replacing IPTp-SP (current policy) by ITNs alone or by a combined intervention in this low transmission setting on economic grounds. The cost per pregnant woman of providing the services was lowest for the IPTp-SP intervention (US$0.79 per woman) followed by ITNs (US$1.71) and the combined intervention of IPTp-SP + ITNs (US$2.48). The relative cost-effectiveness of antenatal distribution of ITNs might improve if the cost savings accruing from continued use of a long-lasting insecticidal net after pregnancy as well as positive externalities were also taken into account, and this warrants further study.