BACKGROUND: Partners of heart failure (HF) patients are important in the course and management of the disease. It is unclear whether HF affects the quality of life (QoL) of partners as much as it affects the QoL of patients. METHODS AND RESULTS: The study aims to determine the influence of role (patient or partner) and gender on quality of life (QoL) and depressive symptoms in HF patients and their partners. Using a cross-sectional design, data on demographics, QoL, and depressive symptoms were collected from 393 HF patients (age, 68+/-11; 76% male) and their partners (age, 67+/-12; 24% male) using questionnaires (Medical Outcome Study 36-item General Health Survey [RAND-36], Cantril Ladder of Life, and Center for Epidemiologic Studies Depression Scale) that were send at home. At a group level HF, patients reported a significantly worse QoL and more depressive symptoms compared with their partners. When examining the influence of role and gender a significant interaction between role and gender was found. QoL in terms of general well-being of female HF partners and female HF patients did not differ (7.0 vs. 6.9), whereas male partners had a significantly higher well-being compared to male HF patients (7.6 vs. 6.8). Most of the RAND-36 domains were explained by role (either being a patient or a partner) with patients having lower scores compared with their partners. However, the RAND-36 domain mental health was mainly explained by gender, with women reporting worse mental health compared with men, independent of their role as a patient or a partner. The same trend was found for the presence of depressive symptoms. CONCLUSIONS: Females, either as patients or as partners are vulnerable in their response to HF in terms of their QoL. The QoL of male partners does not seem to be negatively affected. Supporting couples who are dealing with HF requires different interventions for male and female patients and their partners.