Background: Identifying the objective and subjective aspects of the quality of life (QoL) of institutionalized cognitively impaired older adults (CIOAs) is a challenge. However, it can reveal which aspects of their care require improvement. Aim: The aim of this study was to identify the core aspects of the QoL of CIOAs living in a nursing home (NH) by involving informal and professional caregivers (PCs). Methods: Our sequential, mixed methods study exploring the QoL of CIOAs was based on Lodgson et al’s (2002) quantitative quality of life–Alzheimer’s disease (QoL-AD) questionnaire.Subsequently, a qualitative phase study analyzed perceptions and impressions of QoL using interviews of CIOAs and their most significant informal caregivers (SICs) and PCs. Results: Fifteen CIOAs, 12 SICs, and 2 PCs were recruited. Two-thirds of the older adults were females, overall average age was 86 years (SD=6.1), and all had a severe clinical dementia rating (CDR=3). A high level of comorbidity (measured using the Cumulative Illness Rating Scale for Geriatrics) was significantly associated with a lower QoL-AD score (P=0.046). Higher numbers of visits by SICs or family members had a positive effect on QoL-AD scores (P=0.036). No significant differences were found in overall QoL-AD scores as rated by CIOAs, SICs, and PCs (P=0.080). Combining quantitative and qualitative data analyses revealed four significant themes influencing the QoL of CIOAs: 1) human dignity and acceptance; 2) development and existence; 3) functionality and health; and 4) recognizability and safety. Conclusion: Sequentially using mixed methods proved an appropriate way to examine the QoL of severe CIOAs living in an NH, and these results were compared with the perceptions of informal and PCs. The factors optimizing overall health were visits by SICs and family members, and the major aspect that increases the QoL was freedom of movement inside and outside the NH.