Depression in adults with congenital heart disease is highly prevalent and strongly associated with adverse prognosis. Better management of risk factors for depression may improve clinical outcomes in this population. We conducted a single-site, cross-sectional study of 78 adults with congenital heart disease followed at Washington University School of Medicine. Data considered in the analyses included retrospectively obtained clinical information and patients’ self-assessed psychosocial functioning and health status. To identify the clinical and psychosocial variables associated with depression, we built a stepwise multivariate model to measure the relative contribution of these variables to depression status. The prevalence of depression in our sample was 26%. Our model accounted for approximately 67% of the variability in depression scores. The final model consisted of the Cardiac Denial of Impact Scale, expectations domain of Barriers to Care, and the energy and social domains of the Rand 36-Item Short Form Health Survey. Clinical variables did not predict variability in depression scores. In conclusion, greater cardiac denial and negative expectations of the healthcare team were associated with increased depression symptoms in ACHD.