Background: Quality of Life-Alzheimer's Disease (QOL-AD) is a widely used scale for the study of quality of life in patients with dementia. The aim of this study is the transcultural adaptation and validation of the QOL-AD scale in Portugal. Methods: Translation and transcultural adaptation was performed according to state-of-the-art recommendations. For the validation study, 104 patient/caregiver pairs were enrolled. Patients had mild cognitive impairment or mild-to-moderate dementia (due to Alzheimer's disease or vascular dementia). Participants were recruited in a dementia outpatient clinic setting and a long-term care dementia ward. An additional comparison group of 22 patients without cognitive impairment, and their proxies, was recruited in a family practice outpatient clinic. Sociodemographic information on patients and caregivers was obtained. Acceptability, reliability, and construct validity were analyzed. Results: Internal consistency of the Portuguese version of QOL-AD was good for both patient and caregiver report (Cronbach's alpha = 0.867 and 0.858, respectively). Construct validity was confirmed by the correlation of patient reported QOL-AD with patient geriatric depression scale scores (rho = -0.702, p < 0.001) and satisfaction with life scale scores (rho = 0.543, p < 0.001). Caregiver ratings were correlated with neuropsychiatric inventory (NPI) total score (rho = -0.404, p < 0.001), NPI-distress (rho = -0.346, p < 0.001), and patient Mini-Mental State Examination (rho = 0.319, p < 0.01). QOL-AD patient ratings were higher than caregiver ratings (p < 0.001). Both patient-and caregiver-rated QOL-AD scores were lower in patients with cognitive impairment than in the comparison group without cognitive impairment (p < 0.01). Conclusions: A Portuguese version of QOL-AD with consistent psychometric properties was obtained and is proposed as a useful tool for research and clinical purposes.