Background: Parents of infants with CHD, the most prevalent group of congenital anomalies, experience increased parenting stress levels. These can potentially interfere with the normal parenting process, and with establishing a healthy parent-child relationship, which are important for proper development during infancy. Neurodevelopmental delays are among the major morbidities of children with CHD. The changes in stress over the critical period of infancy (first year of life), and how the stress affects infant development, however, have yet to be studied. Aims: To describe and compare parenting stress levels and changes over time between parents of infants with CHD and parents of healthy infants, during the first year of infants’ life; and to examine associations between parenting stress and infant neurodevelopmental outcomes in these populations. Methods: A secondary analysis of data a larger prospective cohort study (N=241), performed during 2003-2007 at the Children’s Hospital of Philadelphia, included mixed-effects and general linear regression modeling. Findings: Parents of infants with CHD had higher parenting stress than parents of healthy infants on the Child and Parent Domains at three months of age. The stress remained higher on the Demandingness subscale throughout the first year of infants’ life. The change in parenting stress over time significantly differed in parents of infants with CHD and in parents of healthy infants on the Child and Parent Domains, and on the Life Stress. Parents of CHD infants demonstrated decrease in stress over time, and parents of healthy infants generally experienced increase in stress with time. As for the associations between stress and development, findings demonstrate cross-sectional relationships between stress and development, as well as temporal relationships between early stress and later development in both subjects and controls. Conclusions: Findings highlight stressful periods, which may be risky for parents of infants with CHD, and introduce psychosocial/familial aspects as additional contributors to infant development. Family systems intervention may promote parental adaptive coping and productive parenting practices in this population.