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Background: Serum creatinine and cystatin C levels are influenced by different non-renal factors. The difference between the estimated glomerular filtration rates (eGFRdiff) based on these two markers helps assess cardiovascular risk factors unrelated to kidney function. However, its impact on post-ablation atrial fibrillation (AF) recurrence remains unknown., Methods: From July 2017 to February 2023, we prospectively observed 989 consecutive AF patients who underwent radiofrequency ablation. The association between eGFRdiff and post-ablation AF recurrence was analyzed using Kaplan-Meier methods, adjusted Cox regression analysis, and restricted cubic spline (RCS) analysis., Results: During a median follow-up period of 29 months, 326 cases of AF recurrence were detected. Participants were divided into three groups based on eGFRdiff: high (≥ -9.22), medium (-20.98 to -9.22), and low (≤ -20.98). Multivariable Cox proportional hazards models revealed that, compared to the medium eGFRdiff group, individuals in the low eGFRdiff group (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.08-1.94, p < 0.01) and the high eGFRdiff group (HR 1.69, 95% CI 1.27-2.27, p < 0.01) had a significantly increased risk of AF recurrence. RCS analysis demonstrated a U-shaped association between eGFRdiff and AF recurrence. Stratified analyses confirmed the robustness of the core findings across subgroups, except for females. Notably, the geriatric nutritional risk index and the derived neutrophil-to-lymphocyte ratio partially mediated the association between eGFRdiff and high AF recurrence by 5.7% and 10.7%, respectively., Conclusion: eGFRdiff is related to individual nutritional and inflammatory statuses and can be used to predict the risk of AF recurrence. (Clinical trial registration number: ChiCTR-OIN-17013021)., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024 Huang et al.)