Ipratropium, a short-acting anticholinergic bronchodilator, is frequently prescribed for the maintenance treatment of COPD. Tiotropium is a new once-daily bronchodilator. OBJECTIVE: To compare the costs and consequences of tiotropium versus ipratropium in COPD patients with a FEV1 65% of predicted normal. METHODS: The cost-consequence analysis was part of a one-year randomized controlled double-blind clinical trial in the Netherlands and Belgium. Consequences were expressed as the number of COPD exacerbations, the number of patients with a minimal clinically relevant improvement in the St. Georges Respiratory Questionnaire (SGRQ), and the number of effectively treated patients. A societal perspective was adopted when calculating COPD-related direct health-care costs. Multiple imputation (SOLAS) was used to impute all missing data. RESULTS: Tiotropium was associated with a 27% reduction in exacerbations (p = .03). The number of patients with a clinically relevant improvement in SGRQ after 1 year of treatment was 16% higher in tiotropium (p < .001). The proportion of effectively treated patients was 21% higher (p < .001). Across all categories, health-care resource use was consistently lower for tiotropium than for ipratropium. There was a 47% reduction (p = .07) in the number of hospital admissions and a 36% reduction (p = .03) in the number of unscheduled visits to physicians and other care givers. The use of concomitant medication was comparable in both groups. COPD-related health-care costs were estimated to be Euro 1310 in ipratropium and Euro 1065 in tiotropium. Hence, annual savings were estimated to be Euro 245 with a 95% CI ranging from -656 to +167. This estimate excludes the costs of the study medications, since the price of tiotropium still has to be set. CONCLUSION: This cost-consequence analysis favors the new once daily bronchodilator tiotropium over ipratropium on all relevant outcome measures.