This study evaluated whether the effect of tiotropium on the change in trough forced expiratory volume in 1s (FEV1), vs. placebo, is affected by smoking status. In a 3-month, double-blind study in 31 centres in Portugal, 311 (289 completed) patients were randomised to tiotropium 18 microg once daily or placebo. Baseline mean (standard deviation (SD)) FEV1 was 1.11 (0.39) l in the tiotropium group and 1.13 (0.39) l in the placebo group. Patients had an average smoking history of 55 (25.7) pack-years; 80 (26%) were smokers and 224 (74%) were ex-smokers. The primary end-point was change in morning pre-dose (i.e. trough) FEV1 after 12 weeks. Trough FEV1 at 12 weeks was significantly improved with tiotropium vs. placebo: the difference in means was 102 ml, P=0.0011, 95% confidence interval (CI) (41, 164). The difference in means in smokers was 138 ml, P=0.0105, CI (32, 244); in ex-smokers it was 66 ml, P=0.0375, CI (3, 129). The difference between smokers and ex-smokers was not statistically significant (P=0.6982) and may be due to greater variability and differences in disease severity. The significant improvement in lung function in patients treated with tiotropium vs. placebo in both smokers and ex-smokers suggests that tiotropium is an effective and well-tolerated therapy in chronic obstructive pulmonary disease (COPD), regardless of smoking status.