BACKGROUND Smoking during pregnancy has been reported to be associated with a twofold to fourfold increased risk of attention-deficit hyperactivity disorder (ADHD) in the offspring. Genetic and socioeconomic confounders may contribute to this association. The aim of this study was to investigate the association between fetal exposure to maternal smoking during pregnancy and ADHD, taking such potential confounders into consideration. METHODS A register study in a population of 982,856 children, 6-19 years of age, born at term, and residents in Sweden in 2006 was conducted. Logistic regression was used to calculate odds ratios (ORs) of maternal smoking habits during pregnancy on ADHD medication in the 927,007 study subjects where maternal smoking habits were available from the Medical Birth Register in the presence of socioeconomic and parental psychiatric morbidity confounders. To adjust the analysis also for genetic confounding, we used a within-mother between-pregnancy approach in offspring of 26,292 mothers with inconsistent smoking habits (smoking/non-smoking) between pregnancies. RESULTS The OR for ADHD medication in offspring of mothers who smoked >or=10 cigarettes/day was 2.86 (2.66-3.07) in the entire study population after adjustment for sex and age, while this same exposure yielded an OR of only 1.26 (0.95-1.58) when two pregnancies of the same mother were analyzed in a within-subjects design. CONCLUSIONS Smoking during pregnancy has a strong association with ADHD in the offspring in the general Swedish population, but this risk is primarily explained by genetic and socioeconomic confounding.