Background: PDE3/PDE4 inhibitors have emerged as a novel therapeutic strategy for COPD. This trial was conducted to evaluate the efficacy of TQC3721, a dual PDE3/4 inhibitor, in patients with COPD on different background therapies. Methods: COPD patients, with post-bronchodilator FEV₁ 30-70% predicted, were randomized 1:1:1 to receive 3 mg or 6 mg TQC3721, or placebo by nebulized inhalation, twice daily for 4 weeks. Randomization was stratified by background therapy (approximately a 3:7 ratio of LAMA and LABA/LAMA background therapy). The primary endpoint was peak FEV₁ over 4 weeks. Findings: 240 patients were randomized. Improvement of peak FEV₁ at Week 4 from baseline was 194 (95%CI 144-244) mL in the 3mg group, 241 (196-286) mL in the 6mg group and 86 (56-116) mL in the placebo group. erj;66/suppl_69/PA4595/F1F1F1 The LS mean change of peak FEV₁ at Week 4 in the 3mg (100 [41-159] mL) and 6mg (147 [93-201] mL) groups was superior to the placebo group. 6mg treatment significantly improved the LS mean change of peak FEV₁ at Week 4 in the LAMA (239 [130-348] mL) and LABA/LAMA (109 [47- 170] mL) subgroups versus placebo. The incidence of adverse events (AE) in both groups was similar. Interpretation: TQC3721 significantly improved lung function and symptoms compared to placebo with good tolerability. The study supports the further development of TQC3721.