OBJECTIVE: Medication adherence is a recognized problem in older persons and is exacerbated by the factors such as comorbid conditions. The aim of this study was to examine the relationship between self-reported health status and medication adherence in older adults with chronic diseases. METHODS: A longitudinal cohort study was conducted in older adults (aged greater than or equal to 65 years) enrolled in a health maintenance organization. Study sample included patient cohorts with four major chronic diseases: Type 2 Diabetes Mellitus (n=667), Overactive Bladder (n=176), Asthma (n=129), and Psoriasis (n=63). Self-reported health perception, falls, lifestyle, and depressive symptomatology in the pre-enrollment year were measured using a risk-assessment questionnaire. The SF-12 questionnaire assessed the quality of life and the short-form Center for Epidemiologic Studies Depression Scale assessed depression level (0-100). Medication Possession Ratio (MPR) was used as a measure of medication adherence. Multivariate regression analyses were conducted examining predictors of MPR scores. RESULTS: A 0.28-point increase in MPR [Range 0-1] was found in patients receiving oral antidiabetics as compared to patients who did not receive oral antidiabetics (p <0.001). Increased number of comorbidities were associated with decreased adherence (p<0.05). In OAB patients, previous year hospitalization was associated with 0.05-point decrease in MPR for antimuscarinic medication (p <0.05). For asthmatic patients, depressive symptomatology was associated with 0.31-point decrease in MPR (p<0.05). Psoriasis patients with depressive symptoms and those whose physical activity was only moderate were less adherent to topical corticosteroids (both p <0.01). CONCLUSION: Significant associations were found between predictors of health status such as depressive symptoms and decreased medication adherence in elderly patients with chronic diseases. Health status assessments completed at the time of enrollment may have the potential to identify older adults at risk for poor adherence for better intervention.