OBJECTIVE: Even if oral ciprofloxacin is an antibiotic that is commonly used for ambulatory treatment of exacerbations of chronic airway diseases (ECAD), its clinical superiority over other antibiotics remains to be proven. Randomized clinical trials in which efficacy was measured with bacterial eradication and disappearance of symptoms provided unconclusive results. METHODS: Using the administrative databases of the Quebec Health Insurance Plan, we assessed the effectiveness of oral ciprofloxacin in the ambulatory treatment of ECAD among patients aged over 65 years. Within a cohort of 10,820 subjects (mean age of 73 years) followed from 1989 to 1996, we performed a case-control analysis to determine whether oral ciprofloxacin prevents hospitalizations for ECAD. RESULTS: There were 465 cases of hospitalization for ECAD that occurred during the first seven days of therapy and 175 cases that occurred after the 7th day of therapy. After adjusting for markers of disease severity, we found that users of oral ciprofloxacin were less likely to be hospitalized than users of other antibiotics during the early part of therapy (1-7 days) (rate ratio=0.6; 95% CI=0.4-1.0). However, after 7 days of therapy we found that users of ciprofloxacin were more likely to be hospitalized for ECAD (rate ratio=1.7; 95% CI=1.1-3.3). CONCLUSION: Ciprofloxacin was found to be associated with a reduction in hospitalizations for ECAD compared with other antibiotics early in the course of therapy, but with an increase in hospitalizations after 7 days of therapy. The lack of effectiveness in the later part of therapy is likely due, at least in part, to confounding by indication.