Context High cortisol level is known to be associated with osteoporosis, hypertension, diabetes mellitus (DM), susceptibility to infections and depression and may protect against chronic obstructive pulmonary disease. Objective This study assesses the association between cortisol level, 6- to 7·5-year mortality risk and prevalence of chronic diseases. Design/setting/participants Subjects were selected from the Longitudinal Aging Study Amsterdam, an ongoing multidisciplinary cohort study in a general population of older persons (≥65 years). Serum cortisol was measured in 1181 men and women in 1995/1996 (second cycle) and salivary cortisol in 998 men and women in 2001/2002 (fourth cycle). Main outcome measures Six to seven and a half year mortality and prevalence of chronic diseases. Results Men with high salivary morning cortisol had a higher mortality risk than men with low levels [hazard ratio (HR) = 1·63, P = 0·04 for the third vs. the lowest tertile]. Women with high salivary evening cortisol had a higher mortality risk than women with low levels (HR = 1·82, P = 0·04 for the third vs. the lowest tertile). In men, high serum cortisol was independently associated with chronic nonspecific lung disease (CNSLD): odds ratio (OR) = 0·72, P <0·01; hypertension: OR = 1·38, P <0·01; DM: OR = 1·38, P = 0·02. In women, high salivary evening cortisol was independently associated with DM: OR = 1·33, P = 0·01 and CNSLD: OR = 0·58, P = 0·02. No independent association between cortisol and number of chronic diseases was found. Conclusion High salivary cortisol levels are associated with increased mortality risk in a general older population. High cortisol levels are associated with higher risks of hypertension and DM and lower risk of CNSLD.