Objective: Through clinical studies and animal experiments, we explored the expression of BRD4 in patients with NVAF and its role in the postoperative recurrence and occurrence of atrial fibrosis. Methods: 74 patients with NVAF and 73 patients with PSVT were included. The BRD4 levels of the patients were measured. Thirty-Six Sprague Dawley(SD) rats were randomly divided into three groups. The incidence and duration of AF in each group were recorded. Masson’s trichrome staining was performed. Western blot was used to detect the expression of BRD4, TGF-β1, P-Smad2/3, Smad2/3, Smad7, Cx43, and type III collagen in each group. Results: The BRD4 levels were significantly higher in patients with AF than those of PSVT,especially in patients with persistent AF and postoperative recurrence of AF and AF with left atrial low voltage( P < 0.05). The collagen volume fraction and average induced rate of AF and average duration of AF and levels of BRD4, TGF-β1, P-Smad2/3, Smad2/3, and type III collagen were significantly highest in the AF + CTL group than those of the CTL group and AF + JQ-1 group( P < 0.05). Conclusions: BRD4 was correlated with AF and atrial fibrosis. Inhibition of BRD4 expression significantly improved the degree of left atrial fibrosis in rats with AF and reduced the incidence of AF and the duration of AF. BRD4 may be involved in atrial fibrosis and remodeling through the TGF-β1/Smad signaling pathway, thus participating in the occurrence and maintenance of AF.