The relationship between perceived social support and domain-specific health-related quality of life (HRQOL) was examined in a sample of cardiac catheterization patients after considering age, gender, race, education, and coronary artery disease (CAD) severity. Data was collected on 4,278 cardiac catheterization patients (63% males) and included 1,215 patients with non-significant CAD and 3,063 patients who had significant CAD ( > or = 75% stenosis of at least one major coronary artery). Among the patients with significant CAD, 2,721 were classified as low disease severity and 342 were considered high disease severity. Regression models indicated that a lack of social support was associated with significantly lower levels of HRQOL across all eight SF-36 HRQOL domains after considering disease severity and other demographic factors. The models also indicated that social support and other relevant variables interacted across various HRQOL domains. Physical function and physical role function were lower with age, whereas mental health, emotional role function, and vitality were higher with age. Females reported lower HRQOL than males across all domains. Minority patients reported lower levels of HRQOL than white patients across four domains. Increased disease severity was related to lower levels among four of the eight HRQOL domains. The observed interactions of social support with minority status, disease severity, and education suggest that a subset of individuals may suffer lower levels of HRQOL. These individuals may subsequently require the greatest degree of care and potentially benefit most from intervention.