Introduction: Although retrograde intrarenal surgery (RIRS) is being performed with increasing frequency, there are only a limited number of studies about the learning curve (LC). This study aimed to analyze the LC of RIRS for five surgeons who underwent the same training. Materials and Methods: The data of the 410 patients who underwent RIRS between April 2017 and 2022 in a single institution, which were performed consecutively by five surgeons, were analyzed. All 50 cases performed by each surgeon were included and numbered consecutively and separately, according to the date of the operation. The combined stone-free rate (SFR) was calculated for each surgeon’s cases in the same row, and the LCs were created using moving average and cumulative sum (CUSUM) analyses. Separate multivariable analyses identified each period’s (LC vs. beyond) characteristics. Results: The LCs from the combined SFRs reached a plateau after approximately 50 cases for both the CUSUM and the moving average. The effect of stone burden on SFR was more evident in the first 50 cases compared to subsequent cases in the multivariable analyses (p = 0.001 and p = 0.047, respectively). Case order and stone density were independent factors in the first 50 cases (OR: 1.02 [95% CI 1.00–1.04], p = 0.04 and OR: 0.99 [95% CI 0.99–1.00], p = 0.04) but not significant in subsequent cases (OR: 0.97 [95% CI 0.94–1.00], p = 0.1 and OR: 1.00 [95% CI 0.99–1.00], p = 0.7, respectively). Compared to single locations except the lower calyx, the unfavorable effect of the multiple-stone localization on SFR grew in strength after the 50th case (OR: 0.42 [95% CI 0.23–0.78], p = 0.01 and OR: 0.20 [95% CI 0.09–0.46], p < 0.001, respectively). Conclusions: This is the first study reporting on the RIRS LCs of urology residents. While stone burden, density, and multiple-stone localization were the factors determining SFR in the learning period, after completing the LC, the effect of stone burden weakened and multiple-stone localization became stronger.

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