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ObjectivesHigh school dropout has unfavourable consequences. We examine the association between dropout and mortality and estimate the mediating role of an unfavourable work trajectory.MethodsSubjects born in Norway 1967–1976 were followed up in several national registries. The association between dropping out of high school by age 23 and all-cause and cause-specific mortality 10 years onwards were estimated as hazard ratios (HR), applying Cox regression in confounder-adjusted models. Characteristics relating to different trajectories during follow-up were considered as mediators of dropout effects on survival.ResultsThirty-nine percent out of 396 373 participants were classified as dropouts. All-cause mortality during follow-up was 69 per 1 00 000 person-years (2689 cases). The crude dropout HR was 2.1 (1.9–2.3), being reduced to 1.8 (1.6–2.0) in the confounder-adjusted model. After including the potential mediators in the model, dropouts no longer had an excess mortality compared to non-dropouts (HR 1.0, CI (0.9–1.1)). Mediators relating to financial situation, social benefits and employment accounted for the largest reduction in the association. Deaths caused by overdose and drug dependence were strongly associated with dropout (454 cases; rate 12; confounder-adjusted HR 5.0 (3.8–6.5)). Inclusion of work trajectory factors attenuated the association by 63% (women) and 48% (men).ConclusionsMortality was clearly associated with high school dropout, strongest for drug-related causes. The results suggest that an unfavourable work career following high school dropout could be an important mechanism for this association.