Guidelines recommend percutaneous nephrolithotomy (PCNL) for larger renal stones, but advances in flexible ureteroscopy (f-URS) with a tip-bendable suction ureteral access sheath (S-UAS) have prompted further investigation. Our multicenter, international, randomized controlled trial is investigating whether f-URS with S-UAS is noninferior to mini-PCNL (mPCNL) for renal stones of 2-3 cm. The primary objective is the immediate stone-free rate (SFR). Secondary outcomes include the 3-mo SFR, complication rates, surgical time, hospital stay, auxiliary procedures, and improvements in quality of life. A total of 720 patients from 12 urological centers will be randomized to either f-URS with S-UAS or PCNL. Statistical analyses will include intention-to-treat and per-protocol approaches, with specific methods for normally and non-normally distributed data. Subgroup analyses will focus on stone location and lithotripter types. The significance threshold will be set at p < 0.05. The aim of this trial is to generate high-level evidence regarding the noninferiority of f-URS with S-UAS compared to mPCNL for medium-sized renal stones. The trial is registered on ClinicalTrials.gov as NCT06526390.