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Abstract Background In areas of stable transmission, malaria during pregnancy is associated with severe maternal and foetal outcomes, especially low birth weight (LBW). To prevent these complications, weekly chloroquine (CQ) chemoprophylaxis is now being replaced by intermittent preventive treatment with sulfadoxine-pyrimethamine in West Africa. The prevalence of placental malaria and its burden on LBW were assessed in Benin to evaluate the efficacy of weekly CQ chemoprophylaxis, prior to its replacement by intermittent preventive treatment. Methods In two maternity clinics in Ouidah, an observational study was conducted between April 2004 and April 2005. At each delivery, placental blood smears were examined for malaria infection and women were interviewed on their pregnancy history including CQ intake and dosage. CQ was measured in the urine of a sub-sample (n = 166). Multiple logistic and linear regression were used to assess factors associated with LBW and placental malaria. Results Among 1090 singleton live births, prevalence of placental malaria and LBW were 16% and 17% respectively. After adjustment, there was a non-significant association between placental malaria and LBW (adjusted OR = 1.43; P = 0.10). Multiple linear regression showed a positive association between placental malaria and decreased birth weight in primigravidae. More than 98% of the women reported regular chemoprophylaxis and CQ was detectable in 99% of urine samples. Protection from LBW was high in women reporting regular CQ prophylaxis, with a strong duration-effect relationship (test for linear trend: P < 0,001). Conclusion Despite high parasite resistance and limited effect on placental malaria, a CQ chemoprophylaxis taken at adequate doses showed to be still effective in reducing LBW in Benin.