Left-ventricular (LV) pacing with optimized atrio-ventricular (AV) timing may provide similar or greater benefit in comparison with bi-ventricular (BiV) pacing in a subset of cardiac resynchronization therapy (CRT) patients with sinus rhythm and preserved AV conduction. We hypothesized that the optimal device AV delays during LV pacing can be predicted using electrocardiogram (ECG) and device electrograms. METHODS AND RESULTS PATIENTS: (n= 55) with sinus rhythm and PR interval < 300 ms had their CRT devices programmed to atrial and LV pacing with a range of AVs as well as to echocardiographically optimized BiV and no ventricular pacing. At each setting, LV function was evaluated using echocardiography and AVs corresponding to the highest LV ejection fraction (LVEF), lowest LV end-systolic volume (LVESV), and the average of the two (by EF and ESV) were determined. Correlation between the optimal AVs and the following intervals was investigated: intrinsic QRS duration (QRSs), intervals from atrial pacing (Ap) to right-ventricular (RV) sensing (Ap-RVs), from RV sensing to LV activation (RVs-LVs), and from LV pacing to RV sensing (LVp-RVs). Optimal AVs moderately correlated with intrinsic Ap-RVs interval, whereas other parameters showed weak or no correlation. The best correlation (R = 0.66, P< 0.0001) was between the optimal AV delay according to EF and ESV, and Ap-RVs interval. Programming of AVs during LV pacing to the shortest of 70% of the intrinsic Ap-RVs interval, or Ap-RVs--40 ms resulted in significant improvement in LV function similar to that in case of BiV. Optimal AV during LV pacing can be approximated from the intrinsic AV conduction time.