BACKGROUND: Cross-sectional studies suggest an association between eczema and mental health problems, but the temporal relationship is unclear. OBJECTIVE: To assess the association between infant-onset eczema and mental health problems in a prospective study. METHODS: Between 1995 and 1998, a birth cohort study was recruited and followed until age 10 years. Physician-diagnosed eczema, comorbidities, and a broad set of environmental exposures were assessed at age 1, 2, 3, 4, 6, and 10 years. First, we investigated the association between infant-onset eczema (age 1-2 years) and mental health problems at age 10 years according to the Strengths and Difficulties Questionnaire. Second, we analyzed the likelihood of mental health problems at age 10 years in relation to the course of eczema. RESULTS: A total of 2916 infants were eligible for analysis. Compared with participants never diagnosed as having eczema, children with infant-onset eczema had a significantly increased risk for possible/probable mental health problems (Strengths and Difficulties Questionnaire total score) at age 10 years (odds ratio, 1.49; 95% CI, 1.13-1.96) and for emotional symptoms (odds ratio, 1.62; 95% CI, 1.25-2.09). Eczema limited to infancy predicted a significantly higher risk for conduct problems at age 10 years. The strength of the association between eczema and emotional problems at age 10 years increased with increasing eczema persistence. CONCLUSION: Infants with eczema are at increased risk for mental health problems at age 10 years. Even if cleared afterward, eczema at age 1 to 2 years may cause persistent emotional and behavioral difficulties.