Background Angiotensin receptor neprilysin inhibitors (ARNI; sacubitril/valsartan combination) decrease morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Increased P-wave duration and P-wave dispersion (P-d) reflect prolongation of atrial conduction and correlate with atrial fibrillation. Here, we aimed to assess the effects of switching from valsartan to ARNI treatment on the basis of P-wave indices. Methods A total of 28 patients with HFrEF (mean age, 64.8 +/- 10.6 years; 18 males, 78.6% ischemic etiology) were included. All patients had New York Heart Association functional class II-III, left ventricular ejection fraction <= 35%, and had been switched from valsartan to ARNI treatment. Standard 12-lead electrocardiograms from patients on valsartan treatment and electrocardiograms 1 month after ARNI treatment were analyzed; heart rate, maximum P-wave duration (P-max), minimum P-wave duration (P-min), and P-d were calculated. Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores and N-terminal pro-brain natriuretic peptide (NT-proBNP) values were recorded. Results The P-max (135.6 +/- 32.1ms vs. 116.1 +/- 14.1ms, p= 0.041) and P-d (33.6 +/- 7.9 vs. 28.6 +/- 5.3, p= 0.006) values were significantly reduced after ARNI treatment. Furthermore, ARNI treatment was associated with an improvement in MLWHFQ scores (31.2 +/- 6.2ms vs. 23.2 +/- 7.0ms, p< 0.001) and with a reduction in NT-proBNP values (1827.3 +/- 1287.3pg/ml vs. 1074.4 +/- 692.3pg/ml, p< 0.001). There were moderately positive correlations between the reduction in P-d and the improvement in MLWHFQ scores (r= 0.408, p= 0.031) and the reduction in NT-proBNP values (r= 0.499, p= 0.007) Conclusion Switching to ARNI treatment alters P-d and P-max favorably in patients with HFrEF. The reduction in atrial inhomogeneous conduction assessed by P-d was correlated with clinical improvement and reduced NT-proBNP levels in patients with HFrEF.