Abstract Objective: The purpose of the study was to evaluate the sociodemographic and clinical variables modifying the smoking-related risk of low birth weight (<2500 g). Method: This case-control study included a population of 967 singleton low birth weight deliveries and 967 selected controls. Unconditional logistic regression analysis was used to test statistical significance of the interactions between smoking in pregnancy and other risk factors for low birth weight. Results: Increasing maternal age and parity potentiate the smoking-related risk of a low birth weight infant. The effect of maternal smoking on the risk of low birth weight was significantly increased in patients with a history of previous spontaneous abortion (excess risk 2.30, 95% C.I. 1.24–4.27) and in patients of high compared with patients of intermediate or low social class (excess risk 1.97, 95% C.I. 1.1–3.57). Smokers with less than two prenatal visits per trimester were at significantly greater risk of delivering a low birth weight infant (excess risk 2.36, 95% C.I. 1.14–4.87) than their counterparts with more frequent prenatal visits. Among clinical variables, the effect of maternal smoking on the risk of low birth weight was significantly increased in women with a history of first trimester hemorrhage during the current pregnancy (excess risk 2.67, 95% C.I. 1.30–5.49). Conclusions: The smoking-related risk of low birth weight is very high in some subgroups of women. Identification of these subgroups could be important for prenatal counseling.