Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patient's existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking. Objective: The aim of the study was to compare the inhaled beta 2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II). Methods: A dose-response curve to formoterol via Turbuhaler ® or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 μg formoterol via Turbuhaler (48-μg cumulative metered dose); B = 200 + 200 + 400 μg salbutamol via pMDI (800-μg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV 1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO 2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded. Results: Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV 1, inspiratory capacity (IC), and forced vital capacity (FVC). There was no significant difference between FEV 1, IC, and FVC values after 48 μg formoterol and 800 μg salbutamol. There was no significant difference in FEV 1 after 24 and 48 μg formoterol and 800 μg salbutamol; however, the difference in FEV 1 after 24 and 48 μg formoterol was significant. Neither heart rate (mean differences from baseline after 48 μg formoterol, 1.9 beats/min [95% CI, −3.4, 7.2] and 800 μg salbutamol, 3.7 beats/min [95% CI, −1.1, 8.5]) nor SpO 2 (mean percentage differences from baseline after 48 μg formoterol, −0.37% [95% CI, −1.22, 0.47] and 800 μg salbutamol, −0.75% [95% CI, −1.73, 0.23]) changed significantly. However, SpO 2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol. Conclusions: In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.