Objective: The purpose of this study is to investigate whether children with congenital esotropia (CET) are more likely than controls to develop mental illness by early adulthood. Design: Retrospective, population-based cohort. Participants: Children (aged <19 years) diagnosed with CET while residing in Olmsted County, Minnesota, from January 1, 1965, to December 31, 1994, and their 1-to-1 non-strabismic birth- and gender-matched controls. Methods: The medical records of patients with esotropia and their controls were retrospectively reviewed for the subsequent development of psychiatric disease. Main Outcome Measures: The development of mental illness and associated comorbidities among patients with CET and their controls. Results: A mental health disorder was diagnosed in 42 (33%) of the 127 patients with CET followed to a mean age of 20.4 years compared with 16% of controls (P = 0.002). Congenital esotropia increased the odds of developing a psychiatric illness 2.6 times (confidence interval, 1.5-4.8) compared with controls. The number of mental health diagnoses (P = 0.019) and the use of psychotropic medications (P = 0.015) were significantly more common among esotropic patients compared with non-strabismic controls. Conclusions: Congenital esotropia, similar to those with intermittent exotropia or convergence insufficiency, increases the odds of developing mental illness by early adulthood 2.6 times compared with controls. The cause of this association does not seem to be associated with premature birth. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.