The role of ipratropium bromide as adjunct therapy to β-agonists in acute asthma is uncertain. We therefore decided to compare the use of 3 mg of salbutamol sulfate alone vs 3 mg salbutamol sulfate with 0.5 mg ipratropium bromide in patients with acute asthma. Patients presenting with acute asthma and an FEV1 less than 70% predicted were randomized to a single combination treatment vs salbutamol alone. All patients received supplemental oxygen and methylprednisolone, 125 mg, IV. Baseline measurements were repeated at 45 and 90 min and these included spirometry, oximetry, and vital signs. A total of 952 patients were screened of whom 342 patients were deemed eligible and were randomized in two groups of 171 patients. The mean (SE) age was 30 years (0.9) vs 29 years (0.7), women, 103 (60.2%) vs 110 (64%), 81 (47.4%) never-smoked vs 83 (48.5%), and duration of asthma in years 16.0 (0.8) vs 16.6 (0.8) were no different in the combination vs salbutamol alone group, respectively. Likewise, there was no significant difference in asthma therapy received in the 24 h prior to presentation; most notably, 151 (88.3%) vs 153 (89.5%) received inhaled β-agonists in that period. Baseline FEV1 was 1.62 L (0.05 L) vs 1.53 L (0.03 L), and median time to treatment being received was no different between both groups. Both treatment arms improved significantly. The increase in FEV1 in the combination group was 0.61 L (0.04 L) and in the salbutamol alone group was 0.52 L (0.04 L) at 90 min. There was a trend toward greater bronchodilatation in the combination group, but this did not reach statistical significance. Fewer hospitalizations, 5.9% vs 11.2%, occurred in the combination group, but this did not reach statistical significance. In conclusion, this large multicenter study failed to show a significantly better response to a combination of salbutamol and ipratropium bromide vs salbutamol alone.