Objective To compare the clinical efficacy and safety of negative pressure flexible sheath，negative pressure rigid sheath，and conventional rigid sheath combined with ureteroscopy in treating ≤3 cm upper urinary tract stones. Methods A retrospective analysis was performed on the clinical data of 128 patients with upper urinary tract stones who underwent ureteroscopy with holmium laser lithotripsy at The First Affiliated Hospital of Chongqing Medical University and The People’s Hospital of Qijiang District in Chongqing between January 2022 and September 2023. Based on the type of sheath used，the patients were divided into three groups：negative pressure flexible sheath（Group 1，n=61），negative pressure rigid sheath（Group 2，n=31），and conventional rigid sheath（Group 3，n=36）. The conventional rigid sheath group and negative pressure rigid sheath group were collectively referred to as the traditional sheath groups. Baseline data and perioperative indicators were compared across the three groups. Results The general information，including sex，age，body mass index，stone diameter，stone type and location，preoperative placement of ureteral stents，and preoperative infection indicators，as well as their hospitalization duration and postoperative hemoglobin decline，showed no significant differences across the three groups. For stones with diameters ≤3 cm，the highest stone clearance rate was observed in the negative pressure flexible sheath group（91.80%），followed by negative pressure rigid sheath group（80.65%） and conventional rigid sheath group（72.22%）. The stone clearance rate of negative pressure flexible sheath group was significantly higher than that of the conventional rigid sheath group（91.80% vs. 72.22%；χ²=4.155，P=0.012）. Additionally，the negative pressure flexible sheath group had the highest stone-free rate，which was significantly higher compared to the traditional sheath groups（73.77% vs. 41.94% vs. 33.33%；χ²=17.486，P<0.001）. When the stone diameter exceeded 2 cm，the negative pressure flexible sheath group had a significantly higher stone-free rate than the traditional sheath groups（72.55% vs. 36% vs. 23.08%；χ²=19.645，P<0.001）. For stones with diameters <2 cm，the negative pressure flexible sheath group had higher stone clearance rate（90.00% vs. 83.33% vs. 90.00%；χ²=0.193，P>0.908） and stone-free rate（80.00% vs. 66.67% vs. 60.00%；χ²=0.963，P>0.618） compared to the traditional sheath groups，although the differences were not significant. The negative pressure flexible sheath group had a longer surgical duration，lower total hospital costs，and a lower incidence of complications. Conclusion Negative pressure flexible sheath provides a higher immediate stone clearance rate，a higher stone-free rate，and a lower postoperative infection risk. The method also reduces the use of stone retrieval baskets and thus saves the costs. Compared to traditional sheaths，negative pressure flexible sheath demonstrates higher efficacy and safety in treating ≤3 cm upper urinary tract stones and is worthy of wider application.