Objective: To explore the curative effect of negative pressure ureteral access sheath (NPUAS) in patients with different compositions of upper urinary tract calculi. Methods: A total of 124 patients with upper urinary tract calculi who underwent NPUAS + flexible ureteral lithotripsy (FURL) were retrospectively enrolled. According to the different stone compositions, they were divided into calcium oxalate stone group (COS group, n=53), uric acid stone group (UAS group, n=32) and calcium phosphate stone group (CPS group, n=39). The perioperative indexes, postoperative pain, laboratory indexes and safety were compared among the three groups. Results: The primary clearance rate of stones, levels of hemoglobin (Hb) and creatinine (SCr) in UAS group were higher than those in COS group and CPS group (P<0.05), the total intraoperative laser energy, peak of negative pressure suction, peak pressure of renal pelvis, use rate of lithotomy basket, operation time, length of hospital stay, score of visual analogue scale (VAS), levels of white blood cell (WBC), C-reactive protein (CRP) and urine leukocyte (LEU) were lower than those in COS group and CPS group (P<0.05). There was no significant difference in secondary operation rate or incidence of complications among the three groups (P>0.05). Conclusion: The curative effect and safety of NPUAS + FURL are good in patients with different compositions of upper urinary tract calculi. However, the effect is better in those with relatively softer uric acid calculi.