Housing adaptations (HA) clients are a heterogeneous group of people with disabilities experiencing restricted performance and participation in everyday life. While health-related quality of life is a common and relevant outcome in health care research, associated factors among HA clients are largely unknown. Thus, the aim of this study was to investigate which factors are associated with health-related quality of life among HA clients in Sweden. The study has a cross-sectional design, using baseline data collected among 224 participants in three municipalities in Sweden. The main outcome was health-related quality of life measured by the EQ-5D. Factors investigated as potentially associated were age, sex, living conditions, cognitive impairment, usability of the home, activities of daily living (ADL) dependence, participation, and fear of falling. The associations were explored using multiple linear regression analysis. Younger age and higher dependence in ADL were associated with lower scores on the EQ-5D. The social aspect of usability in the home had a positive association with the EQ VAS. Results suggest that certain groups of HA clients might be at risk for low health-related quality of life. Knowledge of their characteristics can potentially improve development and implementation of tailored interventions aiming at increasing their health-related quality of life.