BACKGROUND:Depression is a well-established comorbidity of heart disease (HD) and is more prevalent in women than in men. Few studies have examined the gender effect on depression in patients with advanced heart disease prior to open heart surgery (OHS), controlling for cardiac indices. Previous studies indicated the health benefit of optimism but often lacked adjustment for medical confounders. This interdisciplinary study investigated gender differences in pre-OHS depression and the role of medical comorbidities and strength factors. METHOD:Two waves of survey data were collected from 481 patients (mean age = 62, female 42%) along with medical indices in the Society of Thoracic Surgeon's (STS) national database used by all US cardiac surgeons. RESULTS:A t test showed significantly higher levels of pre-OHS depressive symptoms in women than in men. In multivariate analyses, the gender effect on depression vanished after entry of other socio-demographics, medical comorbidities, objectively assessed cardiac indices in the STS database, and psychosocial strength factors. Depressive symptoms linked inversely with dispositional optimism and positively with medical comorbidities and religious/spiritual struggle, but not with any cardiac indices. A mediation analysis supported the role of comorbidities in the gender difference. CONCLUSION:Women with heart disease were more depressed, but the gender difference may be partly explained by multiple comorbid conditions that could complicate disease burden. Reinforcing the literature, optimism, but not other strength factors, appeared to counteract depression after adjusting for health and cardiac conditions. The finding suggests that health providers should be more attentive to overall health of women with heart disease and to the positive expectations of OHS patients.