In recent years, antimicrobial resistance has been increasingly reported. One main concern is the resistance of gram-negative bacteria like E. coli to ciprofloxacin (fluoroquinolones).Gram-negative bacteria are the main cause of community and hospital-acquired urinary tract infections (UTI). We aimed to review and analyze the data on ciprofloxacin resistance in hospital and community-acquired UTI. A literature search of three electronic databases (PubMed, Medline, and Cochrane) was performed. We considered the papers that were published from January 2004 to May 2019. The search yielded a total of 16097 studies besides 31 studies from a manual search. Filtering yielded 1297 relevant full-text papers.Eighty-three papers, equivalent of 99 cohorts, were finally included in this systematic review and in the analysis. The analysis results suggest that pooled ciprofloxacin resistance for community and hospital-acquired E. coli UTI is 0.27 (95% CI 0.246-0.303) and 0.30 (95% CI 0.22-0.38), respectively. Pooled resistance rates according to regions are 0.43 (95% CI 0.31-0.54) for Asia ensued by Africa 0.31 (95% CI 0.22-0.35), the Middle East 0.21(95% CI 0.13-0.30), Europe 0.18 (95% CI 0.13-0.22), and Australia 0.06 (95% CI 0.04-0.08). The pooled estimates revealed that ciprofloxacin resistance was higher in developing countries compared to that in developed countries, 0.35 (95% CI 0.30-0.40) and 0.13 (95% CI 0.10-0.16), respectively. Finally, plotting resistance over time deemed statistically significant (n= 79, r= 0.29, p= 0.038). Our findings suggest that ciprofloxacin resistance among UTI patients is a highly prevalent and serious issue. The suggested risks are low-income, acquiring hospital infection, and falling in highly-vulnerable regions like Asia and Africa. We also shed light on some approaches to correct the perception of patients and general practitioners (GPs) for antibiotic usage. We also suggest ideas to impede the progress of the post-antibiotic era in countries known for high antibiotic resistance.Blocking this enzyme accumulates the supercoiled DNA and impedes organism replication as a result (12). Ciprofloxacin has been the most effective empirical treatment for UTI, but patients are becoming more resistant to it. For example, the resistance raised from 24.9% in 2010 to 40.7% in 2015 among Brazilian patients treated for E.coli UTI (13). Herein, we review and update rates of ciprofloxacin resistance and compare resistance in CA-UTI with that in HA-UTI caused by gram-negative E. coli.Papers with data on prevalence or incidence of ciprofloxacin resistance in CA or HA E.coli UTI were included. The main inclusion criteria were: (1) English articles published between 2004 and 2019 in peer-reviewed journals, (2) studies conducted on either adults or children.Nonrelevant papers with the following characteristics were excluded: (1) grey literature, (2) comments, (3) letters to editors, (4) conference abstracts, (5) reports, (6) theses, (7) non-peer reviewed studies, (8) review articles, and (9) articles with samp...