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Prior studies of quality of life among cardiac patients have examined mostly men. This study evaluated gender differences in quality of life and examined the degree to which social support was associated with quality of life.A sample of 536 patients (35% women) was recruited during a 14-month period from the inpatient cardiology service of a University-based hospital. Participants completed assessments at baseline and at 3-month intervals over the subsequent 12 months, for a total of 5 assessments. Measures at each assessment included quality of life [Mental Component Score (MCS) and Physical Component Score (PCS) from the Medical Outcomes Study—Short Form 36] and social support [Interpersonal Support Evaluation List—Short Form].A total of 410 patients completed the baseline assessment and at least one follow-up, and were included in the data analyses. Linear mixed effects modeling of the MCS score revealed a significant effect of gender (p = .028) and time (p < .001), as well as a significant interaction of gender by social support (p = .009). Modeling of the PCS revealed a significant effect of gender (p = .010) and time (p < .001).Women with cardiac disease indicated significantly lower quality of life than men with cardiac disease over the course of a 12-month longitudinal follow-up. Social support, especially a sense of belonging or companionship, was significantly associated with emotional quality of life (MCS) among women. Strategies to increase social support may be important for health and well-being of women with cardiac disease.