The HandiHaler is a novel breath-actuated dry powder system designed for the delivery of tiotropium 18microg daily in the treatment of COPD. We compared patient ability to use the HandiHaler or metered dose inhaler (MDI) device correctly 4 weeks after receiving brief instructions and device demonstration. A single-blind study was conducted in COPD patients in two centers in Denmark. ALL patients (n = 151) received one placebo capsule via the HandiHaler daily and ipratropium (20 microg) two actuations via the MDI q.i.d. Mean FEV1 for all patients was 1.25 + 0.54 (46% predicted). Twelve instructions establishing proper device use were evaluated for the MDI and Handihaler. Error scores were analyzed by number of patients with less, equal or more errors when using HandiHaler compared to MDI in the total efficacy population (n = 139) and according to those who had not previously used an MDI for at least 12 months (MDI beginners) (n = 74) and those who had used an MDI (MDI experienced) (n = 65). Four weeks after device instruction, a higher proportion of patients in the total population (P < 0.01) had fewer errors with the HandiHaler (35.3%) compared to the MDI (15.1%). The number of errors was equal in 50% of patients. Similar findings were observed in the subgroup of patients who were MDI beginners (42% vs. 11%, P < 0.01) with non-significant trends in favor of the HandiHaler in those patients who were MDI experienced (29.7% vs. 18.9%, P = 0.096). Similar results in favor of HandiHaler were noted across different age and sex strata. The proportion of patients correctly using the device on the first of three attempts was 59.7% and 54.7% for the HandiHaler and MDI, respectively (P = 0.399). In summary, use of the HandiHaler can be easily taught with fewer errors compared to the MDI. Furthermore, patient performance using the HandiHaler was superior to that with an MDI despite prior MDI experience and more frequent usage.