Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38–73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24–1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20–1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19–1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18–1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004–1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00–1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.