Left atrium (LA) modulates left ventricle (LV) filling and cardiac performance. We aimed to assess the effect of heart failure (HF) therapy on LA and LV function, and the relationship between LA/LV improvement and clinical outcome in acute HF with reduced LV ejection fraction (LVEF). Totally, 224 hospitalized patients with acute HF and LVEF < 35% were enrolled and underwent echocardiography. They all received maximal tolerable doses of evidence-based medications. Patients received echocardiographic measurements at each visit including stroke volume, LVEF, LA minimal/maximal volume (LAV_min/LAV_max), LA expansion index, and tissue Doppler parameters. The threshold of LV functional improvement was LVEF > 45% ever occurred before study end. During the mean follow-up of 6.3 years, 62 cases improved well, mean LVEF 49 ± 5% at study end. The reduction of LV filling pressure occurring as early as 2 weeks later, LV systolic function improvement took longer (> 1 month). The reductions in LAV_min and LAV_max between initial stabilization and 2 weeks after HF treatment (Initial-2 W) and the increase of LA expansion index (Initial-2 W) were associated independently with LVEF improvement (p 0.002, 0.006, and 0.007, respectively). The best predictor of LVEF improvement was LAV_min reduction (Initial-2 W) > 5 ml with 77% sensitivity, 76% specificity. Cox proportional hazard regression analyses for cardiovascular events revealed LVEF improvement reduced 74% of events (hazard ratio 0.264, 95% CI 0.192–0.607, p < 0.0001); and LA expansion index (per 1% increase) reduced 14% of events (hazard ratio 0.862, 95% CI 0.771–0.959, p < 0.0001). The early reduction of LAV (Initial-2 W), especially LAV_min, is a powerful early predictor of LVEF improvement. Its occurrence reduces cardiovascular events significantly. ClinicalTrials.gov number: NCT01307722.