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Background The efficacy of levofloxacin and ciprofloxacin in the treatment of urinary tract infection is not clear yet. This study perform a meta-analysis to explore the differences between the two against urinary tract infection (UTI). Methods A computerized literature search was conducted of the databases of PubMed, Medline, Embase, and the Cochrane Library. All the retrieved literatures were randomized comparative studies of levofloxacin and ciprofloxacin. The included studies were screened according to the standard of nanofiltration. The risk of bias was assessed with RevMan 5.3.5 software. The treatment effect index and incidence of adverse reactions index were established and compared via meta-analysis. Results A total of 5 studies were included, involving 2,877 patients overall. The results showed that levofloxacin was more effective than ciprofloxacin, but the difference between the 2 drugs was not statistically significant [odds ratio (OR) =1.18, 95% confidence interval (CI): 0.94 to 1.46, P=0.15]. There was also no statistical significance in the rate of adverse reactions between the 2 drugs (OR =0.91, 95% CI: 0.78 to 1.07, P=0.27). Discussion In the treatment of UTI, the efficacy and safety of levofloxacin and ciprofloxacin are similar statistically. If bacterial resistance is discovered after the treatment of one of the drugs, the other drug might become an alternative.