© 2014 Published on behalf of the European Society of Cardiology. Aims To compare the effects on left ventricular (LV) function of right ventricular (RV) septal pacing vs. cardiac resynchronization therapy (CRT) in patients with an indication for the latter. Cardiac resynchronization therapy is an effective therapy in patients with drug-refractory heart failure. Despite advances in implantation techniques, LV lead placement can be impossible in up to 10% of cases. We, therefore, assessed the effects of RV septal pacing from mid septum (RVmIVS) and outflow tract (RVOT) on cardiac performance, in comparison with CRT. Methods and results Twenty-two patients scheduled for CRT underwent dual-chamber temporary pacing. The ventricular lead was placed at the RV apex (RVA), RVmIVS, and RVOT in random order. Comprehensive echocardiography was performed in a baseline AAI mode and then at each RV position in dual chamber pacemaker function (D pacing, D sensing, D dual responses) mode and repeated on the next day following CRT implantation. Right ventricular apex pacing did not change any of the assessed echocardiography parameters. Both RVmIVS and RVOT pacing increased LV ejection fraction (EF): 29 ± 7% at baseline vs. 32 ± 6% (P = 0.02) and 32 ± 5% (P = 0.04) with RVmIVS and RVOT pacing, respectively. Similarly, the dyssynchrony index (Ts-SD) decreased: 50 ± 19 ms at baseline vs. 39 ± 17 ms (P = 0.04) and 37 ± 17 ms (P = 0.006) with RVmIVS and RVOT pacing, respectively. Cardiac resynchronization therapy further improved LVEF and Ts-SD to 36 ± 7% and 34 ± 15 ms, respectively, however, only LVEF was significantly higher compared with RVmIVS and RVOT pacing (P = 0.03 and P = 0.01 respectively). There were no significant differences in either LVEF or Ts-SD between RVmIVS and RVOT. Conclusion Right ventricular septal pacing from mid septum or RVOT pacing improves LVEF and LV synchrony in CRT candidates. Further improvement in LVEF was achieved by CRT, which remains the 'gold standard' therapy in these patients. However, RV septal pacing is worthy of further study as an alternative strategy when LV lead implantation fails.