BACKGROUND: It is well known that maternal smoking during pregnancy and maternal pre-pregnancy overweight have opposite effects on the infants' birth weight. We report on the association of the combination between both risk factors and the infants' birth weight. METHODS: We studied 3241 infants born at term in the PIAMA birth cohort. Maternal smoking during pregnancy and pre-pregnancy height and weight were self-reported. Multivariable regression analysis was performed to assess the associations between infants of mothers who only smoked during pregnancy, who only had pre-pregnancy overweight and who had both risk factors simultaneously, on term birth weight and the risk of being SGA or LGA. RESULTS: Of 3241 infants, 421 infants (13%) were born to smoking, non-overweight mothers, 514 (15.8%) to non-smoking, overweight mothers, 129 (4%) to smoking and overweight mothers and 2177 (67%) to non-smoking, non-overweight mothers (reference group). Infants of mothers who smoked and also had pre-pregnancy overweight had similar term birth weight (- 26.6 g, 95%CI: - 113.0, 59.8), SGA risk (OR = 1.06, 95%CI: 0.56, 2.04), and LGA risk (OR = 1.09, 95%CI: 0.61, 1.96) as the reference group. CONCLUSIONS: Our findings suggested that the effects of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants' birth weight cancel each other out. Therefore, birth weight may not be a good indicator of an infant's health status in perinatal practice because it may mask potential health risks due to these maternal risk factors when both present together.