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Numerous studies have investigated factors associated with osteoarthritis (OA), but few have investigated their effects on psychological problems and health-related quality of life in older adults with OA. We aimed to investigate factors associated with OA and their influence on health-related quality of life in older adults with OA. Among 1394 participants aged ≥65 years, 952 and 442 were categorized into the OA and non-OA groups, respectively. Comprehensive data on demographic characteristics, medical conditions, health-related quality of life, blood test results, and nutritional intake were obtained. Univariate and multivariate logistic regression analyses were used to evaluate the odds ratio for factors associated with OA, including age (odds ratio (OR), 1.038; p = 0.020), female sex (OR, 5.692; p < 0.001), body mass index (OR, 1.108; p < 0.001), hypertension (OR, 1.451; p < 0.050), hyperlipidemia (OR, 1.725; p = 0.001), osteoporosis (OR, 2.451; p < 0.001), and depression (OR, 2.358; p = 0.041). The OA group showed a significantly lower subjective health status (p < 0.001) and higher difficulty in mobility (p < 0.001) and pain/discomfort (p = 0.010) than the non-OA group. The sleeping hours were significantly shorter in the OA group than those in the non-OA group (p = 0.013). OA was a significant contributing factor for unfavorable health-related quality of life in older adults. Controlling the factors associated with OA should be prioritized, and health-related quality of life should be monitored in older adults with OA.