OBJECTIVES: Tiotropium is a once-daily inhaled anticholinergic maintenance treatment with demonstrated effectiveness in chronic obstructive pulmonary disease (COPD). We aimed to compare persistence of tiotropium-use with other respiratory drugs in COPD in current clinical practice. METHODS: The PHARMO database includes, among others, drug-dispensing and hospital discharge records for >2 million subjects in the Netherlands. All probable COPD-patients were identified by new respiratory drug use (age >54 yrs) or COPD-hospitalizations. New users of tiotropium, ipratropium, long-acting beta-agonists (LABAs), or fixed combination of inhaled corticosteroids and LABA (ICS&LABA), in 1998-2003, were included in the study. Persistence was assessed quarterly during the first year of follow-up. Patients with a proportion of days covered (PDC) ≥80% were considered persistent. Persistence was analysed using generalised estimating equations model. RESULTS: About 37% of new users of tiotropium continued treatment for one year, compared with 14% for ipratropium, 13% for LABA, and 17% for ICS&LABA. Multivariate analyses showed that tiotropium-users were 2-3 times more persistent with their therapy than patients using ipratropium (relative risk [RR]: 2.0; 95% confidence interval [CI]: 1.8-2.3), LABA (RR: 2.9; 95%CI: 2.4-3.6), or ICS&LABA (RR: 2.4; 95%CI: 2.1-2.8), respectively. Male gender, age >70 years, pulmonologist as first prescriber, prior use of other respiratory drugs, and previous hospitalization for COPD were all associated with enhanced persistence with the initial drug-therapy. CONCLUSIONS: Persistence with tiotropium was increased compared to other respiratory drugs in COPD in clinical practice. Additional research is required to understand the reasons for these higher persistence levels. Enhanced treatment persistence may offer benefits to both patients and society in terms of decreased morbidity and costs.