OBJECTIVES: The risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with (OSA) antibiotics was evaluated in a historical population based cohort study comprising patients using maintenance medication for obstructive lung disease. METHODS: The Pharmo database includes drug dispensing records of more than 2 million subjects in The Netherlands. Eligible were patients >or=50 years who in 2003 were dispensed >or=2 prescriptions of daily used inhaled beta(2) agonists, anticholinergics and/or corticosteroids, and experienced at least one exacerbation before 1 January 2006. Exacerbation was defined as a prescription of OS or OSA. The times to the second and third exacerbations were compared using Kaplan-Meier survival analysis. Independent determinants of new exacerbations were identified using multivariable Cox recurrent event survival analysis. RESULTS: Of 49,599 patients using maintenance medication, 18 928 had at least one exacerbation; in 52%, antibiotics had been added. The OS and OSA groups were comparable for potential confounding factors. Median time to the second exacerbation was 321 days in the OS group and 418 days in the OSA group (p<0.001); and between the second and third exacerbation 127 vs 240 days (p<0.001). The protective effect of OSA was most pronounced during the first 3 months following treatment (hazard ratio (HR) 0.62; 99% CI 0.60 to 0.65). In the OSA group, mortality during follow-up was lower (HR 0.82; 99% CI 0.66 to 0.98). CONCLUSION: Treatment with antibiotics in addition to oral corticosteroids was associated with a longer time to the next exacerbation, and a decreased risk of developing a new exacerbation.