Background Several studies have investigated the association between native QRS duration (QRSd) or QRS narrowing and response to biventricular pacing. However, their results have been conflicting. The aim of our study was to determine the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who undergo cardiac resynchronization therapy (CRT) implantation. Methods and results We included 311 patients in whom a CRT device was implanted in accordance with current guidelines for CRT. On implantation, the native QRS, the QRSd and the QI during CRT were measured. After 6 months, 220 (71%) patients showed a 10% reduction in LVESV. The median [25th–75th] QI was 14.3% [7.2–21.4] and was significantly related to reverse remodeling (r = + 0.22; 95%CI: 0.11–0.32, p = 0.0001). The cut-off value of QI that best predicted LV reverse remodeling after 6 months of CRT was 12.5% (sensitivity = 63.6%, specificity = 57.1%, area under the curve = 0.633, p = 0.0002). The time to the event death or cardiovascular hospitalization was significantly longer among patients with QI > 12.5% (log-rank test, p = 0.0155), with a hazard ratio (HR) of 0.3 [95%CI: 0.11–0.78]. In the multivariate regression model adjusted for baseline parameters, a 10% increment in QI (HR = 0.61[0.44–0.83], p = 0.002) remained significantly associated with CRT response. Conclusions Patients with a larger decrease in QRSd after CRT initiation showed greater echocardiographic reverse remodeling and better outcome from death or cardiovascular hospitalization. QI is an easy-to-measure variable that could be used to predict CRT response at the time of pacing site selection or pacing configuration programming.