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This study aimed to identify and compare differences in temperament and maternal stress between infants with complex congenital heart disease and healthy controls at 3 months of age.Study sample was drawn from an existing longitudinal study examining growth in infants with congenital heart disease when compared with healthy controls. Infant temperament and parental stress were measured in 129 mother-infant dyads. Inclusion criteria for infants with congenital heart disease were ≥36-week postmenstrual age, ≥2500 g at birth, surgery in first 6 weeks of life, and no major congenital anomalies or genetic syndromes. The Early Infancy Temperament Questionnaire and Parent Stress Index were the assessment tools used.Infants with single ventricular (SV) physiology were more negative in mood (F = 7.14, p < .001) and less distractible (F = 5.00, p < .008) than the biventricular physiology or Control (C) infant groups. The demands of care for infants with congenital heart disease were a source of stress when compared with Control infants (p < .05). Five of 6 subscales of the Child Domain were significant sources of stress in the SV group compared with biventricle and Control groups. Negative mood and difficulty to soothe were predictors for Child Domain and Total Life Stress in SV infants.The demands of parenting an irritable infant with SV physiology put these mothers at risk for high levels of stress. Results suggest the need for predischarge anticipatory guidance for parents to better understand and respond to the behavioral style of their infants, in particular, infants with SV physiology.