Background Left ventricular (LV) remodelling is a major mechanism underlying disease progression in patients with heart failure (HF) with reduced ejection fraction (EF). Previous studies that LVEF improvement and reverse remodelling can be achieved after therapy with Sacubitril/Valsartan in real-world settings. Therefore, we sought to investigate possible predictors of LV remodelling, in particular echocardiographic parameters derived by Tissue Doppler Imaging. Methods Patients with chronic HF, LV dysfunction (EF < 35%), NYHA class II–III were followed up between September 2016 and January 2019. All patients underwent clinical and echocardiography follow up at baseline and after 12 months of therapy with sacubitril/valsartan. Results Fifty-four consecutive outpatients were enrolled in the study. At follow-up visit LVEF (38 ± 9 vs. 30 ± 5%, p < 0.0001), LVEDD (61 ± 8 vs. 62 ± 8 mm, p = 0.0085), LVESV (114 ± 57 vs. 130 ± 56 mm3, p = 0.0001), mitral regurgitation severity (1 ± 1 vs. 2 ± 1, p < 0.0001), and left atrial area (23 ± 6 vs. 24 ± 6 mm2, p = 0.0121) changed compared to the baseline value. Changes in LVEF (follow up vs baseline) correlated with baseline levels of heart rate (r = 0.24, p = 0.048), LVEDD (r= −0.33, p = 0.004), LVEDV (r= −0.39, p = 0.001), LVESV (r = 0.37, p = 0.002), and changes in LVESV (r=−0.34, p = 0.006). Correlations remained significant even after correction at multivariate analysis including age and gender. Conclusions Treatment with sacubitril/valsartan in patients with systolic dysfunction is associated with an improvement in LVEF in a real world scenario. Smaller LV volumes are associated with better reverse LV remodelling.