Patients with asthma often show increased airway hyperreactivity and mucus hypersecretion. Although beta2-agonist therapy is one of the most common and effective ways used to relieve airway obstruction, the use of a positive expiratory pressure device (PEPD) is also effective in mucus clearance. However, no previously reported study has examined the effectiveness of these two therapies used in combination. This study assessed the effectiveness of a PEPD on beta2-agonist nebulization therapy by measuring the pulmonary function before and after nebulization therapy in 54 asthmatic patients. The results show that the use of PEPD after beta2-agonist nebulization therapy improved pulmonary function compared with the use of beta2-agonist nebulization therapy alone, as shown by the increases in forced midexpiratory flow and forced vital capacity (FVC). Patients with forced expiratory volume in 1 sec (FEV1) below 85% FVC obtained a significant improvement in FEV1 and FVC after using PEPD. When PEPD was used before beta2-agonist nebulization therapy, there were no obvious direct bronchodilative effects. The use of PEPD after beta2-agonist therapy, however, significantly enhanced the bronchodilative effect of beta2-agonist therapy in patients with an FEV1 below 85% FVC. The additional effect of PEPD use in improving pulmonary function after beta2-agonist nebulization therapy might be a result of an enhancement in mucus clearance.