The prevalence of gastroesophageal reflux disease (GERD) is increasing in patients with asthma and the effect of proton pump inhibitor therapy on asthma outcome has shown variable results. The aim of this study was to determine the efficacy of omeprazole in the treatment of asthma and improvement of pulmonary function in adolescents with GERD. Thirty-six consecutive patients (range, 13-20 years old) with moderate persistent asthma and GERD were recruited on regular follow-up in Mashhad City. The case group included 18 patients who received oral omeprazole (20 mg twice a day for 6 weeks) and the control group included 18 patients who received placebo. A pulmonary function test was examined in two groups immediately before and 6 weeks after medication. The symptoms of GERD were significantly improved with omeprazole in the case group. After 6 weeks of study, the mean values of forced vital capacity, forced expiratory volume in 1 second, and peak expiratory flow rate were higher in patients treated with omeprazole (p<0.0001). Treatment by omeprazole is effective for treatment of asthmatic patients with GERD.