[Objective] To explore the efficacy of disposable flexible ureteroscopic lithotripsy (FURL) with flexible vacuum-assisted ureteral access sheath (FV-UAS) in the treatment of 2-3 cm upper urinary tract stones, so as to provide reference for the treatment selection. [Methods] Clinical data of 178 patients with upper urinary tract stones who received FURL or minimally invasive percutaneous nephrolithotomy (MPCNL) at our hospital during Apr. 2022 and Oct. 2023 were retrospectively analyzed. The patients were divided into FV-UAS group (n=90, received FV-UAS combined with diaposable FURL treatment) and MPCNL group (n=88, received MPCNL). The general information, perioperative data, and postoperative stone-free rate (SFR) of the two groups were compared. [Results] All operations were successfully completed. The operation time was significantly longer in the FV-UAS group than in the MPCNL group [(66.5±6.7) min vs. (63.9±7.4) min, P=0.015]. However, the intraoperative hemoglobin reduction [(7.3±3.1)g/L vs.(11.4±5.9)g/L], postoperative hospital stay (P<0.001) [(2.2±0.7)d vs.(5.4±1.3)d], and visual analogue score (VAS) [(2.7±0.9)vs.(5.6±1.1)] were significantly lower in the FV-UAS group than in the MPCNL group (P<0.001). The incidence of persistent gross hematuria was significantly higher in the MPCNL group than in the FV-UAS group (12.5% vs. 3.3%, P=0.023). The FV-UAS group had a similar postoperative immediate (83.3%) and final SFR (95.6%) to those of the MPCNL group (89.8%, 96.6%, P>0.05). [Conclusion] The combination of FURL with FV-UAS for 2-3 cm upper urinary tract stones has a higher SFR and a lower complication rate.Patients experience endurable pain and fast recovery, which is worth promoting and applying in clinical practice.