Background: Pleural effusion refractory to diuretic treatment is frequent in advanced heart failure. Therapeutic thoracentesis is a time-honored practice, recently made simpler and safer by guidance with lung ultrasound. To assess the feasibility and clinical impact of lung ultrasound-driven therapeutic thoracentesis in refractory heart failure.Methods and results: In a single-centre retrospective analysis we recruited 373 patients with heart failure with reduced ejection fraction (26 ± 12%), New York Heart Association class ≥3, and pleural effusion ≥ moderate at lung ultrasound. All patients underwent lung ultrasound-guided therapeutic thoracentesis. Total of 462 lung ultrasound-guided therapeutic thoracentesis procedures were successfully performed without complications. Evacuated pleural fluid by passive drainage was 1030 ± 534 mL. The maximal interpleural space was 73.6 ± 15.6 mm before, and 12.4 ± 3.1 mm after therapeutic thoracentesis (p < .001). Therapeutic thoracentesis induced an immediate symptomatic improvement in all patients, with New York Heart Association class decrease from 3.84 ± 0.37 pre- to 2.7 ± 0.55 post-therapeutic thoracentesis (p <.001). The improvement was long-lasting (for weeks/months) in 89% of patients. The 6-min walking test was 52 ± 29 m before, and 287 ± 56 m one month after therapeutic thoracentesis (p < .05).Conclusion: Lung ultrasound-driven therapeutic thoracentesis of pleural effusion in decompensated heart failure patients is feasible, safe, and efficient. Therapeutic thoracentesis induces immediate and substantial symptomatic relief followed by long-lasting improvement.