<sec> <title>Objectives</title> <p>Menopause is a well-known risk factor for accelerating cognitive aging in women. This study aimed to assess differences in cognitive function and health-related quality of life (HRQOL) according to menopausal status to determine whether the menopause significantly affects the relationship between cognitive function and HRQOL.</p></sec> <sec> <title>Methods</title> <p>This was a cross-sectional comparative study with a convenience sample of 178 Korean women including 89 naturally menopausal women (65 ± 10 years) and 89 non-menopausal women (45 ± 8 years) who met the eligibility criteria and completed neuropsychological tests and self-report questionnaires about their HRQOL, cognitive function, depression, and sleep quality. Multiple regression analyses were performed within and between groups according to menopausal status.</p></sec> <sec> <title>Results</title> <p>Menopausal women had significantly worse scores on neuropsychological performance and HRQOL than non-menopausal women. A better neuropsychological performance (β = 0.34) was solely associated with a better HRQOL in menopausal women, whilst socioeconomic variables were associated with HRQOL in non-menopausal women.</p></sec> <sec> <title>Conclusion</title> <p>Menopause is an important risk factor for HRQOL, and the association between cognition and HRQOL may differ according to menopausal status. When developing programs for target groups to improve daily functioning and HRQOL, healthcare professionals need to pay more attention to this relationship.</p></sec>