Objective To confirm the factor structure of the Parental Stress Scale (PSS) and examine its validity in parents whose children have chronic health conditions. Background Parents who have a child with a chronic illness report more stress than parents of healthy children. However, information is lacking on whether the PSS demonstrates adequate psychometric properties in this population. Method Data came from a convenience sample of 50 parents whose children (aged 6–16 years) were newly diagnosed with asthma, diabetes, epilepsy, food allergy, or juvenile arthritis. Confirmatory factor analysis was used to replicate the factor structure of the PSS. Analyses were bootstrapped to reduce potential sample bias. Results The factor structure of the PSS was validated and demonstrated adequate internal consistency, α = .84. There was evidence of convergent validity with family functioning, r = –.51, parental anxiety, r = .44, and depression, r = .35. Discriminant analyses showed low, nonstatistical correlations with domains of child quality of life, r = –.07 to –.18. The PSS did not differentiate between those with and without psychiatric disorders. Conclusion The PSS is valid and reliable in parents of children with chronic health conditions. Implications Having established robust psychometric properties of the PSS, research is needed to extend its utility and routine use in clinical and public health settings.