About 30% of patients treated with cardiac resynchronization therapy (CRT) do not respond to treatment. The aim of this study was to identify clinical predictors of lack of improvement in patients receiving CRT. From 197 consecutive patients scheduled to receive CRT, 143 fulfilled the inclusion criteria. Mean age was 68 +/- 7 years and 79% were men. Heart failure was due to ischemic heart disease in 49 patients (34%). Mean QRS duration was 165 +/- 26 ms, and left ventricular ejection fraction was 27 +/- 7%. Nonresponder patients were defined as those who died of heart failure, underwent heart transplantation, or did not increase the distance walked in 6 minutes >10%. At 6-month follow-up, there were 28 nonresponders (20%). Among nonresponders, 2 patients received a heart transplantation and 9 patients died of heart failure. In logistic regression analysis, independent predictors of lack of response to CRT were ischemic heart disease (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.2 to 7; p = 0.023), severe mitral regurgitation (OR 3.5, 95% CI 1.3 to 9; p = 0.014), and left ventricular end-diastolic diameter > or =75 mm (OR 3.1, 95% CI 1.1 to 8; p = 0.026). Patients with these 3 predictors had a probability response of 27%.