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Objectives. We examined the association between psychiatric disorders and tobacco use during pregnancy. Methods. Data were derived from a population-based cohort of 744 pregnant African American and White low-income women living in urban and rural areas. The Diagnostic Interview Schedule was used to assess women for 20 different psychiatric disorders. Results. In comparison with nonusers, persistent tobacco users (women who had used tobacco after confirmation of their pregnancy) and nonpersistent users (women who had used tobacco but not after pregnancy confirmation) were 2.5 and 2 times as likely to have a psychiatric disorder. Twenty-five percent of persistent users had at least 1 of the following diagnoses: generalized anxiety disorder, bipolar I disorder, oppositional disorder, drug abuse or dependence, and attention deficit–hyperactivity disorder. Conclusions. In this cohort study, 5 diagnoses were more prevalent among persistent tobacco users than among nonusers, suggesting that several psychiatric disorders contribute to difficulty discontinuing tobacco use during pregnancy. Smoking cessation efforts focusing on pregnant women may need to address co-occurring psychiatric disorders if they are to be successful.