Antimalarial chemoprophylaxis during pregnancy significantly increases the birth weight of babies born to primigravidae, but coverage in sub-Saharan Africa is very limited. This analysis assessed whether increasing coverage is justified on cost-effectiveness grounds. A standardized modeling framework was used to estimate ranges for the cost per discounted year of life lost averted by weekly chloroquine chemoprophylaxis and intermittent sulfadoxine-pyrimethamine (SP) treatment for primigravidae in an operational setting with moderate to high malaria transmission. The SP regimen was found to be more cost-effective than the chloroquine regimen, because of both lower costs and higher compliance. Both regimens appear to be a good value for money in comparison with other methods of malaria control and based on rough cost-effectiveness guidelines for low-income countries, even with high levels of drug resistance. However, extending the SP regimen to all gravidae and increasing the number of doses per pregnancy could make the intervention significantly less cost-effective.