Mothers of children with congenital heart disease (CHD) experience high parenting stress that affects both mothers and children. The purpose was to examine the relationship between coping self-efficacy and parenting stress in mothers of children with CHD and to identify the factors related to parenting stress. Data were collected using a self-reporting questionnaire from 100 mothers whose children, aged 0 to 12, had been diagnosed with CHD. The Coping Self-Efficacy scale was used to measure coping self-efficacy, and Pediatric Inventory for Parents was used to measure the parenting stress. Multiple linear regression analysis was conducted to investigate the factors related to parenting stress. Higher parenting stress was related to lower coping self-efficacy to obtain social support and having any other children. Interventions that consider factors related to parenting stress and to enhance coping self-efficacy is required. Effective practice could be delivered by paying more attention to mothers with less supporters and those who have other dependent children.