Background: The aim of the present study is to clarify whether biased symptom perception towards heart symptoms may explain a reduced quality of life in patients with congenital heart disease (ConHD). The present study tested the hypothesis that the combination of ConHD and high trait anxiety increases the perception of heart symptoms during acute stress. Methods: 25 patients and 24 healthy participants completed a stressful computer task. Participant's heart and non-heart symptoms were measured after stress and after relaxation. Heart rate, blood pressure, respiratory rate, and arterial partial pressure of CO, were monitored continuously. Results: In line with the prediction, a combination of high trait anxiety and ConHD resulted in an increased perception of specifically heart symptoms during stress. Moreover, the increased perception of heart symptoms could not be explained by acute heart dysfunction. Conclusions: Heart dysfunction is not the only cause of an increased perception of heart symptoms. A history of disease experience in combination with high trait anxiety may increase the perception of heart symptoms during stress and may eventually result in an increased risk of developing a reduced quality of life.