Abstract Objectives This study was conducted to assess the safety and effectiveness of cardiac resynchronization therapy (CRT) when combined with an implantable cardioverter defibrillator (ICD). Background Long-term outcome of CRT was measured in patients with symptomatic heart failure (HF), intraventricular conduction delay, and malignant ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) requiring therapy from an ICD. Methods Patients (n = 490) were implanted with a device capable of providing both CRT and ICD therapy and randomized to CRT (n = 245) or control (no CRT, n = 245) for up to six months. The primary end point was progression of HF, defined as all-cause mortality, hospitalization for HF, and VT/VF requiring device intervention. Secondary end points included peak oxygen consumption (VO 2), 6-min walk (6 MW), New York Heart Association (NYHA) class, quality of life (QOL), and echocardiographic analysis. Results A 15% reduction in HF progression was observed, but this was statistically insignificant (p = 0.35). The CRT, however, significantly improved peak VO 2 (0.8 ml/kg/min vs. 0.0 ml/kg/min, p = 0.030) and 6 MW (35 m vs. 15 m, p = 0.043). Changes in NYHA class (p = 0.10) and QOL (p = 0.40) were not statistically significant. The CRT demonstrated significant reductions in ventricular dimensions (left ventricular internal diameter in diastole = −3.4 mm vs. −0.3 mm, p < 0.001 and left ventricular internal diameter in systole = −4.0 mm vs. −0.7 mm, p < 0.001) and improvement in left ventricular ejection fraction (5.1% vs. 2.8%, p = 0.020). A subgroup of patients with advanced HF (NYHA class III/IV) consistently demonstrated improvement across all functional status end points. Conclusions The CRT improved functional status in patients indicated for an ICD who also have symptomatic HF and intraventricular conduction delay.