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Background: Adolescent mental health difficulties are increasing over time. However, it is not known whether their adulthood health and socio-economic sequelae are changing over time. Methods: Participants (N = 31 349) are from two prospective national birth cohort studies: 1958 National Child Development Study (n = 16 091) and the 1970 British Cohort Study (n = 15 258). Adolescent mental health was operationalised both as traditional internalising and externalising factors and a hierarchical bi-factor. Associations between adolescent psychopathology and age 42 health and wellbeing (mental health, general health, life satisfaction), social (cohabitation, voting behaviour) and economic (education and employment) outcomes are estimated using linear and logistic multivariable regressions across cohorts, controlling for a wide range of early life potential confounding factors. Results: The prevalence of adolescent mental health difficulties increased and their associations with midlife health, wellbeing, social and economic outcomes became more severe or remained similar between those born in 1958 and 1970. For instance, a stronger association with adolescent mental health difficulties was found for those born in 1970 for midlife psychological distress [odds ratio (OR) 1970 = 1.82 (1.65–1.99), OR 1958 = 1.60 (1.43–1.79)], cohabitation [OR 1970 = 0.64 (0.59–0.70), OR 1958 = 0.79 (0.72–0.87)], and professional occupations [OR 1970 = 0.75 (0.67–0.84), OR 1958 = 1.05 (0.88–1.24)]. The associations of externalising symptoms with later outcomes were mainly explained by their shared variance with internalising symptoms. Conclusion: The widening of mental health-based inequalities in midlife outcomes further supports the need to recognise that secular increases in adolescent mental health symptoms is a public health challenge with measurable negative consequences through the life-course. Increased public health efforts to minimise adverse outcomes are needed. [ABSTRACT FROM AUTHOR]