Objective: We aimed to analyze the relationship between optimism and quality of life (QoL) among informal caregivers of patients with dementia (PWD).; Design: In this cross-sectional study, a hierarchical multiple linear regression analysis was used to determine the association between optimism and caregiver's QoL after controlling the effect of different covariates, including burden.; Participants: A sample of 130 PWD and their informal caregivers underwent a comprehensive protocol of assessment.; Measurements: Caregivers completed the Battery of Generalized Expectancies of Control Scales, the Zarit Burden Interview, and the World Health Organization Quality of Life-Brief as measure of QoL. Optimism was estimated based on the combination of three expectancies of control, namely, self-efficacy, contingency, and success.; Results: QoL correlated positively with optimism and negatively with burden. Optimism predicted each dimension of QoL, even after controlling for the effect of sociodemographic, care-recipients' clinical covariates, and burden in all models.; Conclusion: Optimism consistently predicted well-being and QoL in informal caregivers of PWD.