The object of this study was to examine the role of emotional reactivity in infants with congenital heart defects (CHD) in relation to their mothers' symptoms of postnatal depression. The study population was drawn from the Norwegian country-wide CHD registry from the Department of Pediatric Cardiology at Oslo University Hospital and the Norwegian Mother and Child Cohort Study. Mother-infant dyads with mild/moderate or severe CHD (n=242) were assessed with a 6-item short version (EPDS-6) of the Edinburgh Postnatal Depression Scale and the Infant Characteristic Questionnaire's fussy/difficult subscale (ICQ-D/F-7) at 6 months postpartum. When adjusting for infant emotional reactivity, mothers of infants with severe CHD showed significantly elevated symptoms of postnatal depression 6 months postpartum (odds ratio=2.22) compared to the mothers of infants with mild/moderate CHD. The results identify severe CHD in infants as a predictor of heightened symptoms of postnatal depression in mothers, independent of the infant's emotional reactivity. Although a causal direction underlying the association could not be determined, the possible, negative reciprocal relationships between severe CHD in infants, high levels of emotional reactivity in infants, and symptoms of maternal postnatal depression are considered.