Background There is a paucity of research describing health‐related quality of life (HRQOL) in older adults considered for advanced heart failure surgical therapies. Using data from our SUSTAIN‐IT (Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support) study, we aimed to compare HRQOL among 3 groups of older (60–80 years) patients with heart failure before heart transplantation (HT) or long‐term mechanical circulatory support (MCS) and identify factors associated with HRQOL: (1) HT candidates with MCS, (2) HT candidates without MCS, or (3) candidates ineligible for HT and scheduled for long‐term MCS. Methods and Results Patients from 13 US sites completed assessments, including self‐reported measures of HRQOL (EuroQol‐5 Dimension Questionnaire, Kansas City Cardiomyopathy Questionnaire–12), depressive symptoms (Personal Health Questionnaire–8), anxiety (State‐Trait Anxiety Inventory–state form), cognitive status (Montreal Cognitive Assessment), and performance‐based measures (6‐minute walk test and 5‐m gait speed). Analyses included ANOVA, χ ² tests, Fisher’s exact tests, and linear regression. The sample included 393 patients; the majority of patients were White men and married. Long‐term MCS candidates (n=154) were significantly older and had more comorbidities and a higher New York Heart Association class than HT candidates with MCS (n=118) and HT candidates without MCS (n=121). Long‐term MCS candidates had worse HRQOL than HT candidates with and without MCS (EQ‐5D visual analog scale scores, 46±23 versus 68±18 versus 54±23 [ P <0.001] and Kansas City Cardiomyopathy Questionnaire–12 overall summary scores, 35±21 versus 60±21 versus 49±22 [ P <0.001], respectively). In multivariable analyses, lower 6‐minute walk distance, higher New York Heart Association class, depressive symptoms, and not being an HT candidate with MCS were significantly associated with worse overall HRQOL. Conclusions Our findings demonstrate important differences in overall and domain‐specific HRQOL of older patients with heart failure before HT or long‐term MCS. Understanding HRQOL differences may guide decisions toward more appropriate and personalized advanced heart failure therapies.