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Aims Left ventricular (LV) lead positioning at the site of delayed electrical activation is associated with better response to cardiac resynchronization therapy (CRT). We hypothesized that a long electrical conduction delay between right ventricular (RV) and coronary sinus (CS) leads during RV pacing (RLD index) is correlated with a better clinical outcome Methods and results RLD is measured intraprocedurally, during RV pacing, as the time interval between the intracardiac electrograms of RV and CS leads. Initially, we did a prove-of-concept, feasibility, acute study in 97 patients who underwent CRT implantation. The CS lead position was assessed in the 40° right anterior oblique and 40° left anterior oblique views and assigned to one of 11 prespecified segments of a schematic eyeball depiction of the LV walls. Acute outcomes were QRS width during biventricular (BIV) pacing. The longest RLD were found in the basal and mid lateral segments; these accounted for 82% and 78%, respectively, of the total QRS width (%RLD). %RLD was inversely correlated with BIV-paced QRS (P = 0.0001). A similar slope was present either in the 78 patients with preserved atrioventricular (AV) conduction and in the 19 without AV conduction (− 0.34 vs − 0.27, P = 0.7). Conclusion We showed that RLD can be used to guide lead placement at the time of CRT implantation and that it is correlated with BIV-QRS width, an indirect predictor of clinical outcome. Based on these findings we started the prospective, multicenter Optimal Pacing SITE 2 (OPSITE 2) trial with the objective to demonstrate a relationship between RLD and clinical outcomes assessed as death, hospitalization for heart failure, New York Heart Association class, and clinical composite score. The protocol is provided.