<p>This research investigated the relationship between serum Syndecan-1 levels and myocardial fibrosis (MF) and major adverse cardiovascular events (MACEs) in elderly patients with atrial fibrillation (AF). Elderly patients with AF were divided into MF (<i>n</i> = 162) and N-MF (<i>n</i> = 89) groups. During 5-year follow-up, 78 patients with MACEs formed the MACEs group, and 173 without MACEs formed the N-MACEs group. Spearman correlation analysis was performed. Multivariate Cox regression and Kaplan–Meier curves were conducted, and ROC curves were plotted. Serum Syndecan-1 was elevated in the MF group versus the N-MF group. Serum Syndecan-1 levels in AF patients showed moderate positive correlations with both sST2 (<i>r</i> = 0.569) and PINP (<i>r</i> = 0.446). Serum Syndecan-1 showed diagnostic value for MF in patients with AF, with an AUC of 0.810. Moreover, combined detection with sST2 and PINP further achieved an AUC of 0.872. Serum Syndecan-1 levels were elevated in the MACE group compared to the N-MACEs group, and serum Syndecan-1 demonstrated discriminatory value for 5-year MACEs (AUC = 0.832). Serum Syndecan-1 (<i>HR</i> = 1.049) was independently associated with 5-year MACEs in AF patients. The risk associated with Syndecan-1 was more pronounced in patients with paroxysmalAF. After adjusting for sST2, NT-proBNP, LVEF, and MF, Syndecan-1 was independently associated with MACEs in patients with heart failure (<i>P</i> = 0.021). Elevated serum Syndecan-1 levels are associated with MF and MACEs in AF patients, suggesting its potential value as a biomarker for discriminating MF and MACEs in AF patients.</p>