Background: During sleep some individuals can develop a disease called sleep apnea that affects 5 to 20% of general population. The old treatment regimens available were invasive upper airway surgery and incompliant oral devices. Montelukast reduces adenoidal hypertrophy causing the air to flow without obstruction and gives effective results such as obstructive sleep apnea (OSA) treatment. Most of the researches have explored children with no enough information about adult OSA patients. This study aimed at exploring the clinical response to montelukast in patients with OSA. Methodology: A prospective before and after study was conducted in an outpatient pulmonology clinic in Amman, Jordan from September 2019 to December 2020. Inclusion criteria were adults aged ? 21 years diagnosed for OSA, on a standard nocturnal polysomnography (PSG). Patients were excluded if they missed 3 doses continuously, had craniofacial anomalies, genetic diseases, neuromuscular diseases or were taking any medication to treat nasal symptoms or allergies. Patients were assigned to receive oral montelukast (10 mg daily). 12 weeks is the duration of treatment. All patients at the commencement of the study underwent PSG to establish baseline data. A post-treatment PSG was obtained at the 12-week interval. The primary study endpoint was the change in apnea hypoapnea index (AHI) between sleep studies performed at the end of the medication treatment periods. Secondary endpoints were snore index (SI), body mass index (BMI) reduction, total sleep time (TST), and SpO2 saturation nadir compared before and after treatment periods. Results: A total of 48 patients participated in the study. The mean age was 44.5 (11.8) years. Most of them (79.2%; n= 38) were males. The average BMI of the patients decreased by 14.9% after the treatment (p<0.001). All clinical parameters related to PSG test showed a statistically significant improvement after montelukast treatment (respiratory analysis parameters, snore analysis parameters, O2 saturation parameters, position change index, and heart rate parameters) p<0.05. Conclusions: Montelukast therapy showed positive outcome results in patients with obstructive sleep apnea. Further studies on larger scale are warranted to confirm our findings.