Objectives: To evaluate the psychometric attributes of the Spanish version of the Quality of Life-Alzheimer's Disease Scale (QoL–AD) in institutionalized patients and family caregivers in Spain. Method: 101 patients (88.1% women; mean age, 83.2 ± 6.3) with Alzheimer's disease (AD) (n = 82) and mixed dementia (n = 19) and their closest family caregivers. Patient-related variables included severity of dementia, cognitive status, perceived general health, quality of life, behavior, apathy, depression, and functional status. QoL–AD acceptability, reliability, and construct validity were analyzed. Results: The mean Mini-Mental State Examination (MMSE) score was 7.2 ± 6.1 and Global Deterioration Scale was: stage four (4%); five (21.2%); six (34.3%); and seven (40.4%). Both, QoL–AD patient version (QoL–ADp) (n = 40; MMSE = 12.0 ± 4.5) and QoL–AD caregiver version (QoL–ADc) (n = 101) lacked significant floor and ceiling effects and the Cronbach α index was 0.90 and 0.86, respectively. The corrected item-total correlation was 0.11–0.68 (QoL–ADc) and 0.28–0.84 (QoL–ADp). Stability was satisfactory for QoL–ADp (intraclass correlation coefficient [ICC]=0.83) but low for QoL–ADc (ICC = 0.51); the standard error of measurement was 2.72 and 4.69. Construct validity was moderate/high for QoL–ADc (QUALID=−0.43; EQ-5D = 0.65), but lower for QoL–ADp. No significant correlations were observed between QoL–ADp and patient variables or QoL–ADc. A low to high association (r = 0.18–0.55) was obtained between QoL–ADc and patient-related measures of neuropsychiatric, function, and cognitive status. Conclusion: Differences in their psychometric attributes, and discrepancy between them, were found for QoL–ADp and QoL–ADc. In patients with AD and advanced dementia, the QoL perceived by the patient could be based on a construct that is different from the traditional QoL construct.