Aims: The aim of this study was to compare the variability and sensitivity of impulse oscillometry (R5, X5 and RF), plethysmography (Raw and sGaw) and spirometry (FEV1, FVC and MMEF) in order to determine the most powerful technique for assessing bronchodilation in COPD clinical trials. Methods: Twenty-four patients with COPD had impulse oscillometry, plethysmography and spirometry measured twice 30 mins apart, to determine variability. Then ascending doses of salbutamol (20, 50, 100, 200, 400 and 800 μg) were given and the same measurements made after each dose. Significant changes greater than variability were determined for each performed measurement (expressed as mean percentage improvement with 95% CI). Results: Significant effects (P <0.05) were detected after 20 μg by X5 (18.5% CI 9.8-27.2) RF (11.1% CI 7.2-15.0) and sGaw (21.5% CI 10.1-32.9), and after 50 μg by R5 (16.7% CI 10.8-22.5) and Raw (19.7% CI 13.0-26.4). FEV1 was less sensitive, detecting significant bronchodilation at 100 μg (10.2% CI 7.4-12.9). Conclusions: We conclude that impulse oscillometry and plethysmography should be considered the preferred techniques for measuring bronchodilation in COPD clinical trials. © 2004 Blackwell Publishing Ltd.