Objective: To examine the role of potential mediating factors in explaining the IQ-mortality relation. Design, setting and participants: A total of 4316 male former Vietnam-era US army personnel with IQ test results at entry into the service in late adolescence/early adulthood in the 1960/1970s (mean age at entry 20.4 years) participated in a telephone survey and medical examination in middle age (mean age 38.3 years) in 1985-6. They were then followed up for mortality experience for 15 years. Main results: In age-adjusted analyses, higher IQ scores were associated with reduced rates of total mortality (hazard ratio (HR) per SD increase in IQ 0.71; 95% CI 0.63 to 0.81). This relation did not appear to be heavily confounded by early socioeconomic position or ethnicity. The impact of adjusting for some potentially mediating risk indices measured in middle age on the IQ-mortality relation (marital status, alcohol consumption, systolic and diastolic blood pressure, pulse rate, blood glucose, body mass index, psychiatric and somatic illness at medical examination) was negligible (,10% attenuation in risk). Controlling for others (cigarette smoking, lung function) had a modest impact (10-17%). Education (0.79; 0.69 to 0.92), occupational prestige (0.77; 0.68 to 0.88) and income (0.86; 0.75 to 0.98) yielded the greatest attenuation in the IQ-mortality gradient (21-52%); after their collective adjustment, the IQ-mortality link was effectively eliminated (0.92; 0.79 to 1.07). Conclusions: In this cohort, socioeconomic position in middle age might lie on the pathway linking earlier IQ with later mortality risk but might also partly act as a surrogate for cognitive ability.Higher mental ability (denoted here as IQ) in childhood and early adulthood is inversely associated with all-cause mortality rates in populations followed for up to six decades.1 That is, high IQ test scores seem to confer protection against premature death. Importantly, the fact that IQ is measured in the first two decades of life in these studies, and is therefore likely to be pre-morbid, suggests that the IQ-mortality gradient is unlikely to be explained by reverse causality whereby comorbidity, rather than low cognitive function, is generating the relation.Despite several reports of this IQ-mortality association appearing in the past five years, 1 important questions remain. In particular, given that the IQ-mortality association does not seem to be explained by selection bias, statistical chance or confounding by early life factors, 1 particularly socioeconomic position, there has been debate regarding the mechanisms that might underpin this gradient. 2 3 One of the most persuasive is that the IQ-mortality gradient is mediated by established behavioural, biological, socioeconomic and psychological risk factors for premature mortality. A strong prima facie for this explanation can be found in a series of studies of populations followed into middle age showing that higher earlier IQ test scores are associated with a lower prevalence of obesity...