Prenatal exposure to tobacco smoke is suggested as a potential risk factor for autism spectrum disorders (ASD). Previous epidemiological studies of this topic have yielded mixed findings. We performed a case-control study of 3,958 ASD cases and 38,983 controls nested in a large register-based cohort in Sweden. ASD case status was measured using a multisource case ascertainment system. In adjusted results, we found that maternal smoking during pregnancy is not associated with increased risk of ASD regardless of presence or absence of comorbid intellectual disability. Apparent associations were attributable to confounding by sociodemographic characteristics of parents such as education, income, and occupation.