This study focused on the relative contribution of heart failure (HF) disease severity, depression, and comorbid anxiety to quality of life for 96 ambulatory HF veterans (48 with and 48 without depressive symptoms). Primary analyses sought to predict HF quality of life using constructs including depression symptoms, comorbid anxiety symptoms, HF severity, medical-illness burden, and demographic factors. Multiple regression procedures found 3 significant predictors of better quality of life, including HF severity (beta = -13.33, p < .001), depressive symptoms (beta = -2.34, p = .003), and age (beta = 0.76, p < .01). These results suggest that disease severity and depression, but not necessarily comorbid anxiety, significantly affect quality of life for HF patients. As HF is a progressive, deteriorating condition, mental health interventions, especially those that target depression, might offer opportunities for improved quality of life for HF patients.