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Objective: Our primary aim is to perform the external validation of the current scoring systems in predicting stone-free status (SFS) after retrograde intrarenal surgery (RIRS) for renal stones 2-4 cm and develop a novel scoring system by re-examining possible predictive factors related to SFS., Methods: Patients who underwent RIRS due to renal stones with a cumulative stone diameter of 2-4 cm between January 2017 and March 2021 were retrospectively screened. Residual stones ≤2 mm were defined as clinically insignificant, and these cases were considered to have SFS. Possible predictive factors related to SFS were examined using the multivariate logistic regression analysis. A nomogram and a scoring system were developed using independent predictive variables. The prediction ability of the previous and the new scoring system were evaluated with the ROC analysis., Results: The existing scoring systems were found to be insufficient in predicting SFS (AUC < 0.660 for all). The independent predictors of SFS were identified as stone surface area (OR: 0.991, p < 0.001), stone density (OR: 0.998, p < 0.001), number of stones (OR: 0.365, p = 0.033), and stone localization (p = 0.037). Using these predictive markers, a new scoring system with a score ranging between 4 and 15 was developed. The AUC value for this scoring system was 0.802 (0.734-0.870)., Conclusion: The RUSS, S-ReSC and R.I.R.S. scoring systems and Ito's nomogram failed to predict SFS in stones >2 cm. The SFS predictive ability of our new scoring system was higher in >2 cm stones compared to the other scoring systems., (Copyright © 2022. Published by Elsevier España, S.L.U.)