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Objectives. We examined the relationship between psychosocial antecedents in earlier adolescence and problems related to substance use and related adverse health consequence (e.g., respiratory diseases, neurocognitive symptoms, and general malaise) in adulthood. We specifically focused on parent–child bonding in earlier adolescence and internalizing behaviors in later adolescence and their effects on problems related to substance use in the mid-20s and health problems in the mid-30s. Methods. Our team interviewed a community-based sample of 502 participants over a 30-year period (1975, 1983, 1985–1986, 1997, 2002, and 2005). Results. We found a strong relationship between internalizing behaviors in later adolescence and adverse health consequences in the mid-30s. Internalizing behaviors in later adolescence served as a mediator between low parent–child bonding in earlier adolescence and later adverse health consequences. Problems related to substance use in the late 20s and early 30s were related directly to later adverse health consequences and indirectly as mediators between earlier psychosocial difficulties (i.e., internalizing behaviors, externalizing behaviors, poor ego integration, and maladaptive coping) and later adverse health consequences. Conclusions. Policies and programs that address parent–child bonding and internalizing behaviors should be created to reduce problems related to substance use and, ultimately, later health problems.