OBJECTIVES: To assess the impact of chronic disease and the number of diseases on the various aspects of health-related quality of life (HRQOL) among the elderly in São Paulo, Brazil. METHODS:The SF-36® Health Survey was used to assess the impact of the most prevalent chronic diseases on HRQOL. A cross-sectional and population-based study was carried out with two-stage stratified cluster sampling. Data were obtained from a multicenter health survey administered through household interviews in several municipalities in the state of São Paulo. The study evaluated seven diseases-arthritis, back-pain, depression/anxiety, diabetes, hypertension, osteoporosis, and stroke-and their effects on quality of life. RESULTS: Among the 1 958 elderly individuals (60 years of age or older), 13.6% reported not having any of the illnesses, whereas 45.7% presented three or more chronic conditions. The presence of any of the seven chronic illnesses studied had a significant effect on the scores of nearly all the SF-36® scales. HRQOL achieved lower scores when related to depression/ anxiety, osteoporosis, and stroke. The higher the number of diseases, the greater the negative effect on the SF-36® dimensions. The presence of three or more diseases significantly affected HRQOL in all areas. The bodily pain, general health, and vitality scales were the most affected by diseases. CONCLUSIONS: The study detected a high prevalence of chronic diseases among the elderly population and found that the degree of impact on HRQOL depends on the type of disease. The results highlight the importance of preventing and controlling chronic diseases in order to reduce the number of comorbidities and lessen their impact on HRQOL among the elderly.