Background. Decreased antimicrobial susceptibility after increased antibiotic use is a known phenomenon. Restoration of susceptibility once antimicrobial use is decreased is not self-evident. Our objective was to evaluate, in a community setting, the impact of quinolone restriction on the antimicrobial resistance of E. coli urine isolates. Methods. We conducted a retrospective, quasi-experimental ecological study to assess the proportion of quinolone-susceptible E. coli urine isolates in the periods before, during, and after a nationwide restriction on ciprofloxacin use was implemented. We used an interrupted time interval analysis for outcome evaluation. Results. We found a significant decline in quinolone consumption, measured as defined daily doses (DDDs) per month, between the preintervention and intervention periods (point estimate, -1827.3 DDDs per month; 95% confidence interval [CI], -2248.8 to -1405.9 DDDs per month; P < .001). This decline resulted in a significant decrease in E. coli nonsusceptibility to quinolones, from a mean of 12% in the preintervention period to a mean of 9% in the intervention period (odds ratio, 1.35; P = .014). The improved susceptibility pattern reversed immediately when quinolone consumption rose. Moreover, a highly significant inverse relationship was found between the level of quinolone use (regardless of intervention period) and the susceptibility of E. coli urine isolates to quinolone (odds ratio, 1.70; 95% CI, 1.26-2.28). During the months of highest quinolone use (8321 DDDs per month), the proportion of nonsusceptibility was 14%, whereas during the months of lowest quinolone use (4027 DDDs per month), the proportion of nonsusceptibility was 9%. An average decrease in resistance of 1.16% was observed for each decrease of 1000 DDDs. Conclusion. Reducing quinolone consumption can lead to an immediate increase in the susceptibility of E. coli urine isolates to quinolones.