Abstract: Objective: To examine the personality trait conscientiousness as a risk factor for mortality and to identify candidate explanatory mechanisms.Methods: Participants in the Whitehall II cohort study (N=6800, aged 34 to 55 at recruitment in 1985) completed two self-reported items measuring conscientiousness in 1991–1993 (‘I am overly conscientious’ and ‘I am overly perfectionistic’, Cronbach’s α=.72), the baseline for this study. Age, socio-economic status (SES), social support, health behaviours, physiological variables and minor psychiatric morbidity were also recorded at baseline. The vital status of participants was then monitored for a mean of 17years. All-cause and cause-specific mortality was ascertained through linkage to a national mortality register until January 2010.Results: Each 1standard deviation decrease in conscientiousness was associated with a 10% increase in all-cause (hazard ratio [HR]=1.10, 95% CI 1.003, 1.20) mortality. Patterns were similar for cardiovascular (HR=1.17, 95% CI 0.98, 1.39) and cancer mortality (HR=1.10, 95% CI 0.96, 1.25), not reaching statistical significance. The association with all-cause mortality was attenuated by 5% after adjustment for SES, 13% for health behaviours, 14% for cardiovascular risk factors, 5% for minor psychiatric morbidity, 29% for all variables. Repeating analyses with each item separately and excluding participants who died within five years of personality assessment did not change the results materially.Conclusion: Low conscientiousness in midlife is a risk factor for all-cause mortality. This association is only partly explained by health behaviours, SES, cardiovascular disease risk factors and minor psychiatric morbidity in midlife.