The author examined the relative effects of tooth loss and xerostomia on the oral health-related quality of life of an elderly, medically compromised population, living in a long-term care setting. Data were collected from 225 subjects (mean age: 83 years) via a questionnaire and review of dental charts. Oral health-related quality of life was assessed using self-ratings, satisfaction ratings, an index of chewing capacity, the GOHAI, and OHIP-14. Almost all participants had one or more chronic medical conditions and were taking prescribed medications. Two-thirds of the study group was dentulous with a mean number of 16 remaining teeth. One-third of the participants had scores on a xerostomia index indicating marked oral dryness. In bivariate and multivariate analyses, xerostomia index scores were significantly associated with all oral health-related quality of life outcomes. Dental status was associated with chewing capacity only. The results suggest that xerostomia has an important influence on the well-being and quality of life of this population.