OBJECTIVE: Treatment for acute exacerbation of chronic bronchitis (AECB) frequently consists of antimicrobial therapy. The persistence of recurrent symptoms can lead to substantial morbidity and increased healthcare costs. These factors make it important to consider antimicrobial treatment from an economic as well as a clinical perspective. This study was designed to assess the relative effectiveness and cost of once-daily clarithromycin (CL OD) 500 mg versus amoxycillin/clavulanic acid (AMCL) 625 mg TID in the treatment of AECB. METHODS: Of 250 patients enrolled in this investigator-blind, multicentre, multicountry comparative trial of CL OD and AMCL in adults with AECB, 127 were randomized to treatment with CL OD, and 123 with AMCL. The primary measure of clinical effectiveness was response to therapy. Healthcare resource utilization was monitored from initiation of therapy to 19-23 days after the last study medication. UK costs were applied to resource use aggregated across all countries in the base case analysis. RESULTS: Investigator-defined clinical response rates were similar in the clinically evaluable population (93/106 [88%] CL OD and 85/99 [86%] AMCL, p=0.837). Mean per patient costs were CL OD £120 (95% CI 6-234) and AMCL £146 (95% CI 5-287). Mean length of stay for hospitalised patients was 10.80 days for CL OD versus 15.25 days for AMCL. Both hospitalisation costs and study medication costs were lower for CL OD. CONCLUSIONS: Previous studies have shown favourable cost comparisons for CL OD versus AMCL but these have been based on decision models. Results from this study provide the first evidence of a trend of cost savings for CL OD versus AMCL from a prospective randomised, multicountry trial.