© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.Retrograde intrarenal surgery (RIRS) is one of the minimally invasive main treatment modalities in renal stone disease. There are many factors which affect stone-free rate (SFR). Our study was based on the hypothesis that higher renal parenchymal thickness (RPT) which may include higher average number of nephrons provides better diuresis. We investigated the efficacy of RPT on success of RIRS. This study is a single-centered prospective surgical cohort study. A total of 383 patients were analyzed. Regularly followed 304 patients with unilateral kidney stone at single pole or renal pelvis and who underwent single-session RIRS were included in the final analysis, and the patients’ preoperative and postoperative 1st and 3rd months’ data were evaluated. RPT was measured on the non-contrast computed tomography (CT) images. ROC analysis was performed to estimate the cutoff value of RPT for SFR. Univariate and multivariate logistic regression analyses were used to model the relationship between RPT and SFR after RIRS. ROC analysis revealed the best cutoff value of the RPT for predicting residual stone as 19 mm for both the 1st and 3rd month visits with Youden indexes of 0.397 and 0.406, respectively. To the best of our knowledge, this is the first study which evaluated the effect of RPT on the efficacy of RIRS. RPT measurement is a cost-effective method that can be easily performed on routinely applied non-contrast CT and may have predictive value for the surgical success in patients with nephrolithiasis.