Health-related quality of life (HRQL) was investigated in 211 inhabitants of five residential homes in The Netherlands and was assessed again 1 year later. It was examined (a) if HRQL was related to the presence of specific general medical illnesses, (b) if comorbidity resulted in poorer HRQL, independent of the type of illness, and (c) if HRQL remained stable over time (1 year). We found that the illnesses we investigated contributed only little power to the prediction of HRQL, although some coefficients were significant. Comorbidity was also found to be a significant predictor of several aspects of HRQL, but did not contribute much power either. Several aspects of HRQL (bodily pain, health perceptions, and social functioning) remained stable over time, whereas other aspects (role functioning, activities of daily living) deteriorated. There was a trend indicating that mental health improves over time. Improvement and deterioration on aspects of HRQL were relatively strongly related to the scores on these aspects 1 year earlier, but not to specific illnesses or comorbidity.