This study aims to identify the factors associated with health-related quality of life (HRQOL) among community-dwelling older adults. Baseline and follow-up data from the ‘Appropriate care paths for frail elderly patients: a comprehensive model’ study were analysed. Physical and mental HRQOL were measured by the 12-item Short Form Health Survey (SF-12). Linear regression models were used to evaluate associations between sociodemographic, health, and lifestyle factors and HRQOL. The sample included 661 participants (mean age = 77.4 years; 47% female) from Rotterdam, the Netherlands. Frailty was negatively associated with physical (B = -6.14; P < 0.001) and mental (B = -7.06; P < 0.001) HRQOL. Similarly, participants with a higher score on activities of daily living limitations had lower physical (B = -1.08; P < 0.001) and mental (B = -0.24; P = 0.019) HRQOL. Female sex (B = -2.27; P < 0.001), multimorbidity (B = -2.83; P < 0.001), and a high risk of medication-related problems (B = -3.06; P < 0.001) were associated with reduced physical HRQOL, and loneliness (B = -3.73; P < 0.001) with reduced mental HRQOL. In contrast, higher age (B = 1.88; P = 0.022) and living alone (B = 3.48; P < 0.001) were associated with better mental HRQOL in the multivariate models. The findings of this study imply that future interventions aimed at promoting the health and autonomy of community-dwelling older adults could be tailored to subpopulations with relatively poor self-reported HRQOL, such as frail or lonely older adults.