Background: The benefit of biventricular pacing (BiV) may be substantially affected by optimal lead placement. Aim: To evaluate the importance of right ventricular (RV) lead positioning on clinical outcome of BiV. Methods and results: A total of 99 patients with symptomatic heart failure and implantation of BiV system were included. Position of the left-ventricular (LV) lead was selected based on timing of local endocardial signal within the terminal portion of the QRS complex. RV lead was preferably positioned at the midseptum (n = 74, RVS group) where the earliest RV endocardial signal was recorded. A subgroup of patients had RV lead placed in the apex (n = 25, RVA group). NYHA class, maximum oxygen-uptake (VO 2 max), LV end-diastolic diameter (LVEDD, mm) and ejection fraction were assessed every third month.A trend towards greater improvement in NYHA class and significant increase in VO 2 max was present in the RVS group. Moreover, a significant decrease in LVEDD (DLVEDD) was observed in the RVS group only (À 3.4 T 6.5 mm versus + 1.7 T 6.4 mm in RVA group at 12 months, p = 0.004). No significant correlation between the degree of DLVEDD and QRS narrowing induced by BiV was found. LVEDD reduction was predominantly present in dilated cardiomyopathy. Conclusions: Midseptal positioning of the RV lead appears to promote reverse LV remodelling during cardiac resynchronisation therapy.