Prospective identification of patients most and least likely to respond to cardiac resynchronization therapy (CRT) for congestive heart failure (CHF) will allow clinicians to target this intervention most efficiently. The authors hypothesized that ECG variables including RBBB and indicators of RV dysfunction and extensive prior myocardial infarction would correlate with diminished response to CRT. This study analyzed preimplantation ECGs in 110 patients with ICD indications and CHF due to left ventricular systolic dysfunction randomized to active biventricular pacing in the MIRACLE ICD trial. Clinical and ECG variables on the outcome of change in peak oxygen consumption from baseline to 6 months (Delta-VO2 ) were evaluated. For this cohort, average peak VO2 improved from 13.4 to 14.3 mL/kg per minute. Among clinical variables, the strongest predictors of increasing Delta-VO2 were reduced exercise time and peak VO2 at baseline. A dominant R wave in lead a VR, RBBB, and evidence of prior anterior infarction were each associated with significantly smaller average improvements in Delta-VO2 than their absence in univariate analysis. Alternative ECG criteria, including QRS duration, had no relationship with the outcome. In a multivariate model, only baseline VO2 (beta=-0.3, P=0.001) and ECG evidence of prior anterior infarction (beta=-1.3, P=0.03) were associated with the outcome. ECG markers of anterior infarction and RV dilation may help identify CHF patients unlikely to benefit from biventricular pacing. Further assessment is needed of these and other predictors of therapeutic response to CRT.