Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking (i.e. self-reported or cotinine >50 ng·mL(-1)) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS (i.e. cotinine 20-50 ng·mL(-1)) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76-24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population.