Treatment with short-acting β2-agonists for exacerbations of chronic obstructive pulmonary disease (COPD) results in clinical improvement. It has not been established whether combining short-acting β2-agonists to other bronchodilators is more effective than β2-agonists alone. We conducted a study in patients presenting to the emergency department with exacerbation of COPD. They were randomized to receive nebulized ipratropium bromide (IB group; n = 62) or combined nebulized and intravenous bolus of magnesium sulfate (MgSO4 group; n = 62). All nebulized drugs were administered at 30-minute intervals for 2 hours. Primary outcome included hospital admission, endotracheal intubation, and hospital death rates. Secondary outcome measures were improvement in peak expiratory flow, dyspnea score, and arterial blood gas changes within the first 3 hours. There were no significant differences in primary outcome between MgSO4 and IB groups. Patients given IB average 32 L greater improvement in peak expiratory flow rate compared with magnesium sulfate (95% confidence interval, 19-43 L) at 180 minutes. Simultaneously, there was a significant reduction in PaCO2 compared with baseline values in IB group but not in MgSO4 group. There was a statistically nonsignificant trend toward a decrease in dyspnea score in both groups although adverse events were similar. Although the improvement in peak expiratory flow rate and arterial blood gas favored nebulized IB over magnesium sulfate, there was a nonsignificant difference between both drugs with regard to hospital admission, intubation, and hospital death rates in patients with COPD treated in the emergency department for acute exacerbation.