Background:To verify the appropriate prophylactic agent to prevent ureteroscopic lithotripsy infection, which is safe, effective, convenient, reasonable, and with best pharmacoeconomic benefit ratio, to provide evidence for clinical practice.Methods:This study is a multicenter, open-label, randomized, positive drug-controlled trial design. From January 2019 to December 2021, patients with ureteral calculi who were going to undergo retrograde flexible ureteroscopic lithotripsy were selected from urology departments in 5 research centers. The patients enrolled were randomly divided into the experimental group and the control group according to the random number table by blocking randomization. In the experimental group (Group A), 0.5 g levofloxacin was given 2 to 4 hours before surgery. In the control group (Group B), cephalosporin was injected 30 minutes before surgery. The infectious complications, the incidence of adverse drug reactions and the economic benefit ratio were compared between the 2 groups.Results:A total of 234 cases were enrolled. There was no statistically significant difference between the 2 groups at baseline. Postoperative infection complications were 1.8% in the experimental group, which was significantly lower than 11.2% in control group. The type of infection complication in both groups was asymptomatic bacteriuria. The cost of drugs in the experimental group was 19.89 +/- 13.11 yuan, which was significantly lower than cost of drugs in the control group of 41.75 +/- 30.12 yuan. The levofloxacin application had favorable cost-effectiveness ratio. The difference in safety between 2 groups was not significant.Conclusion:The application of levofloxacin is safe, effective, and low-cost regimen for postureteroscopic lithotripsy infection prevention.