Abstract Background Biventricular pacing (BIV) is gold standard for cardiac resynchronization therapy (CRT). Thirty % of patients result non responder to CRT. Conduction system pacing (CSP) represents a feasible alternative. Interventricular conduction delay (IVCD), as electrical desynchrony marker, is a CRT response predictor. The aim of the study was to assess CRT responder’s incidence when it has been achieved choosing best approach between BIV and CSP according to intraoperative IVCD measurement in patients with HFrEF and LBBB. Methods Ninety-eight patients have been 1:1 randomized in a standard BIV group (control group, CG) and a group in which CRT approach has been chosen based on IVCD evaluation (study group, SG), as reported in Figure 1. If the right ventricular sensed electrogram (RVs)-left ventricular sensed electrogram (LVs) interval was ≥100 ms, the left ventricular lead was left in its original position; otherwise, the lead was removed and CSP was performed instead, as reported in Figure 2. Clinical, EKG and echocardiographic features have been assessed pre- and 6 months post-implant. Echocardiographic and clinical response have been evaluated. Results Twenty-four % of patients in the SG underwent CSP, according to the operative algorithm adopted. CRT responders’ incidence was significantly higher in the SG (echocardiographic criterion: SG 93,9% vs CG 69,8%; clinical criterion SG 87,9% vs CG 62,8%). Patients in SG presented a significant improvement in EF between pre- and post-implant and a significantly reduced End Diastolic Volumes and End Systolic Volumes vs CG. Univariate and multivariate regression analysis showed that enrolment in SG was the only factor consistently associated to CRT response. Conclusion Intraoperative evaluation of IVCD may guide the choice of the best resynchronization approach between BIV and CSP, allowing to achieve a significant improvement of CRT responders’ rate.Figure 1Figure 2