【Objective】 To explore the efficacy of negative pressure ureteral access sheath combined with disposable flexible ureteroscope (UAS+FRUS) in the treatment of renal calculi of 2-3 cm, so as to provide reference for the treatment. 【Methods】 A retrospective analysis was conducted on 130 cases of renal calculi of 2-3 cm treated with surgery in Xiamen Third Hospital during Sep.2021 and Sep.2023, including 68 cases with UAS+FRUS and 62 cases with super-mini percutaneous nephrolithotripsy (SMP).The perioperative indexes and stone-clearance rate (SFR) were compared between the two groups. 【Results】 All operations were successful.There were no statistically significant differences in the total SFR and incidence of complications (5.88% vs. 9.67%) between the two groups 3 days (88.24% vs. 90.32%) and 1 month (91.18% vs. 93.55%) after surgery (P>0.05).For patients with lower calyceal calculi with infundibulopelvic angle (IPA)<45°, the SFR of the UAS + FRUS group was significantly lower than that of the SMP group (57.14% vs.100%, P<0.05).The UAS + FRUS group had a longer operation time than the SMP group \[(104.94 ± 8.79) minutes vs. (77.98±6.60) minutes, P<0.001\], higher hospitalization costs \[(23 112.82±1152.34) yuan vs. (21 975.84±1512.24) yuan, P<0.001\], less postoperative decrease in hemoglobin \[(6.71±2.07) g/L vs. (9.81±4.80) g/L, P<0.001\], and shorter postoperative hospitalization time \[(3.28±0.51) d vs. (5.58±0.71) d, P<0.001\].The UAS + FRUS group had lower postoperative VAS score at 6, 24, and 48 hours than the SMP group \[(6.38±0.69) vs. (7.87±0.88); (3.62±0.73) vs. (5.81±0.83) and (3.12±0.33) vs. (3.81±0.60)\], with statistical significance (P<0.05). 【Conclusion】 Both surgical methods have a high SFR in the treatment of renal calculi of 2-3 cm.SMP has the advantages of short operation time, low hospitalization costs, and high SFR for lower calyx calculi, while UAS+FURS has the advantages of little bleeding, minimal trauma, and short hospital stay.Surgeons can make reasonable choices based on the patients’ condition and willingness, combined with their own surgical experience.