β-blockers (BB) and ivabradine (I) has been shown to be beneficial in heart failure with reduced EF (HFREF). The main benefit of I derives from heart rate reduction (HRR), whereas BB have broader spectrum of action. We conducted this study to evaluate whether HRR plays a major role in the treatment of HFREF in pts on standard therapy. Methods: 180 pts (55 female) 62±9 years with postinfarction HFREF (EF≤35%) on standard therapy with ACEI/ARB, spironolacton, loop diuretics and in sinus rhythm were randomized to two groups to receive nebivolol (N) titrated up to the achievement of the target HRR (THRR) <70 BPM or I titrated to 10mg BID in order to achieve THRR. THRR were achieved in 43 N tolerated pts, and 56 pts on I and the rest received the combination of N and I on order to reach THRR. All pts on N alone and the same number of pts on I or N+I were selected for the study and comprised 3 groups. EchoCG indexes of LV EDV, ESV and LAV, septal E/Em, mean longitudinal LV strain rate (LSR), Tei index (TI) as IVCT+IVRT/ET, as well as the total ischemic burden (TIB) as a total time of ST segment depressions ≥ 1 mm and ≥1 min duration and HRV as a standard deviation of normal RR intervals (SDNN) were measured by 24-hour ECG monitoring at baseline, 90 and 180 days follow up. Results: After 90 days follow up all parameters were similar between groups but significantly improved at the same degree within each group compared with baseline (p < 0.05). After 180 days follow up LV remodeling was better altered, contractility, SDNN parameters significantly improved at the same degree in N and N+I groups compared with I without differences between N and N+I, TIB did not differ between groups (ESVI: N 59.7±7.4 ml/m2 vs N+I 60.5±7.6 ml/m2 vs I 69.8±7.9* ml/m2, *p<0.05; EDVI: N 95.8±9.4 ml/m2 vs N+I 93.4±9.2 ml/m2 vs I 109.4±9.8* ml/m2, *p<0.05; TI: N 0.76±0.24 vs N+I 0.73±0.22 vs I 0.89±0.28*, *p < 0.05; E/Em: N 11.4±4.1 vs N+I 11.1±4.5 vs I 14.8±5.2*, *p < 0.05; TIB: N 35±13 min vs N+I 34±10 min vs I 33±9 min, p=NS; SDNN: N 103.04±15 ms vs N+I 104.06±16 ms vs I 126±18*ms, *p<0.05; LSR: N 1.59±0.16 vs N+I 1.54±0.14, 1.30±0.12*, *p < 0.05). Both N and I were well tolerated by pts throughout follow up. Conclusion: BB or in case of intolerance their combination with I to further reduce HR are more beneficial than reduction of HR at the same degree solely with I. Additional properties of BB are of importance and neurohormonal modulation with HR reduction better alters the course of HF.