ObjectiveOur 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. MethodsPatients 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. ResultsThe 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). ConclusionThe RUSS, S-ReSC and RIRS 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.