Mothers of individuals with Prader-Willi syndrome (PWS) often experience numerous stressors, even when compared to mothers of children with other intellectual and developmental disabilities. Despite this, these mothers show great variability in self-reported life satisfaction. Using data from a longitudinal study of individuals with PWS and their families, the present study analyzed factors related to maternal life satisfaction, both cross-sectionally and over time. Results show that both child factors (e.g., behavior problems, hyperphagia) and maternal factors (e.g., stress, coping style) were significantly related to maternal life satisfaction. However, none of the tested variables predicted change in life satisfaction over time. Research and practice implications are discussed.