〔Abstract〕 Objective To analyze the effects of spironolactone on myocardial fibrosis indexes and matrix metalloproteinase (MMP) family level in patients with atrial fibrillation (AF) after radiofrequency ablation (RFA). Methods Sixty-eight AF patients treated with RFA in the First Affiliated Hospital of Zhengzhou University from December 2020 to March 2023 were selected and divided into a control group (34 cases) and an observation group (34 cases) according to the method of medication. Myocardial fibrosis indexes, MMP family level, inflammation indexes and adverse reactions were compared between the two groups. Results Three months after surgery, the levels of laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP) and aldosterone in the two groups were lower than those before surgery, and the levels of the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). Three months after surgery, the levels of serum MMP-2 and MMP-9 in the two groups were lower than those before surgery, and the levels of the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). Three months after surgery, the levels of serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the two groups were lower than those before surgery, and the levels of the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Spironolactone can improve myocardial fibrosis after RFA in AF patients, regulate the level of MMP family, inhibit the expression of inflammatory factors, and has high safety.