This study investigated the relationships among stress, intrapersonal resiliency factors (self-esteem, locus of control, and optimism) and quality of life [QOL] (physical health and mental health) among caregivers of children with high functioning autism spectrum disorders (HFASDs). Participants consisted of 113 caregivers of children with HFASDs (males = 38.1%, females = 61.9%; age range = 27–62; 93.6% Caucasians) and 47 caregivers of typically developing children (males = 29.8%; females = 70.2%; age range = 30–56; 93.3% Caucasians). They completed a set of self-rating surveys on perceived locus of control, self-esteem, optimism, and QOL. Within-group inferential statistical analyses were applied. For the HFASD group analyses, two simultaneous regression analyses were used to study the independent effects of the three intrapersonal variables on the physical health and mental health QOL of the caregivers. Intrapersonal factors predicted self-reported mental health QOL but not physical health QOL in caregivers of children with HFASDs.