BACKGROUND More than 20% of Medicare beneficiaries receiving cardiac resynchronization therapy defibrillators (CRT-D) have a very wide (>= 180 ms) QRS complex duration (QRSD). Outcomes of CRT-D in these patients are not well-established because they have been underrepresented in clinical trials. OBJECTIVES This study examined outcomes in patients with CRT-D in a very wide QRSD with left bundle branch block (LBBB) versus those without LBBB. METHODS Medicare patients from the Implantable Cardioverter Defibrillator Registry (January 1, 2005, through April 30, 2006) with a CRT-D and confirmed Class I or IIa indications for CRT-D were matched to implantable cardioverter-defibrillator (ICD) patients without CRT despite having Class I or IIa indications for CRT. Mortality and heart failure hospitalizations longer than 4 years with CRT-D versus standard ICDs based on a QRSD and morphology were analyzed. RESULTS We analyzed 24,960 patients. Among those with LBBB, patients with a QRSD >= 180 ms had a greater adjusted survival benefit with CRT-D versus standard ICD (hazard ration [HR] for death: 0.65; 95% confidence interval [CI]: 0.59 to 0.72) compared with those having a QRSD 120 to 149 ms (HR: 0.85; 95% CI: 0.80 to 0.92) and 150 to 179 ms (HR: 0.87; 95% CI: 0.81 to 0.93). CRT-D versus ICD was associated with an improvement in survival in those with LBBB and a QRSD >= 180 ms (adjusted HR for death: 0.78; 95% CI: 0.68 to 0.91), but not in those with LBBB and a QRSD 150 to 179 ms (adjusted HR for death: 1.06; 95% CI: 0.95 to 1.19). CONCLUSIONS Improvements in both survival and heart failure hospitalizations with CRT-D were greatest in patients with a QRSD >= 180 ms with or without LBBB, whereas patients with a QRSD 150 to 179 ms without LBBB had no improvement in survival with CRT-D, and those with a QRSD 150 to 179 ms and LBBB had only a modest improvement. Published by Elsevier on behalf of the American College of Cardiology Foundation.