Background: Although parental stress is higher for children with neurodevelopmental disorders (NDs), it is unclear how this stress compares to more common NDs. The current study compared stress in parents of children with Williams syndrome (WS), Down syndrome (DS) and autism spectrum disorders (ASD). The impact of individual and contextual factors was also explored. Method: Parents of children with WS (n = 107), DS (n = 79) and ASD (n = 79) completed a background questionnaire, a parental stress questionnaire and a satisfaction with life questionnaire. Results: Although all groups displayed similar levels of parental stress, the factors that influenced this stress differed between the groups. There were also differences for life satisfaction and relationships between parental stress and individual and contextual factors. Conclusions: Although parents of children with NDs are not at an increased risk of parental stress, the results suggest that interventions should be syndrome-specific.