Purpose Cardiac resynchronization therapy (CRT) improves outcomes in ambulatory heart failure (HF) patients with New York Heart Association (NYHA) class II-IV symptoms. However, its role in stage D patients, particularly those eligible for heart transplant (HTx) or ventricular assist device (VAD), has not been well characterized. This study investigates the clinical outcomes of patients who were stage D at time of CRT implant, and the potential factors associated with CRT response. Methods and Materials In this retrospective study, medical records of patients referred to the CRT clinic from Jan 2010 to Dec 2011 were reviewed. Patients were included if they met criteria for stage D HF: 1) inotrope-dependent, and/or listed for HTx, 2) peak oxygen consumption (VO2max) <14ml/kg/min, 3) ambulatory NYHA class IV for at least 60 days, or 4) NYHA class IIIB-IV with at least one hospitalization for HF in the past year for intravenous therapies. We excluded patients with LVEF>35% or QRS duration <121ms. Descriptive, independent sample t-test and Chi-square analyses were conducted. Results Fifty-five patients (mean age 63±11yrs, 75% male) met stage D criteria, of whom 50 had successful CRT implant and were followed for an average of 12±8 months. At last follow-up, 42% (21/50) improved by one NYHA class, or had 10% increase in VO2max or absolute EF; 36% (18/50) were unchanged; 22% (11/50) worsened by one NYHA class or died. CRT response was established by 6 months and did not change over time. Left bundle-branch block and paced QRS morphology at baseline were associated with clinical improvement (91vs.61%, p<0.05). Overall, 28% (14/50) met the composite end-point of HTx, VAD or death; the majority of these patients (10/14) had CRT implanted <12 months before reaching the composite end-point. Conclusions Stage D patients appear to have a lower response rate to CRT than the general HF population. QRS morphology may predict CRT response in these patients. The decision to implant CRT in HTx/VAD eligible stage D patients should include careful consideration of the potential limited benefits.