Objective: To assess the efficacy of adding Slow-Release Theophylline to the regular treatment of Chronic Obstructive Pulmonary Disease (COPD) patients. The safety of Theophylline was also assessed as a secondary endpoint.Methods: Prospective observational study of one hundred and nine patients, with moderate to very severe COPD, and treated in the pulmonology clinic at King Hussein Medical Center, between August 2014 and March 2015. Exclusion criteria included: acute exacerbation of COPD within the last 3 months; use of oral corticosteroids within the last 4 weeks; upper or lower respiratory tract infection within the last 4 weeks; recent unstable angina or arrhythmias; epilepsy; concurrent use of medications that might interact with Theophylline and excessive alcohol consumption. After enrolment, Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC), oxygenation at rest using 2 different pulse oximeters and level of disability assessed by the Medical Research Council dyspnoea scale were evaluated. A fixed dose of oral Theophylline was added to their regular treatment, as Theophylline (Quibron-T SR) 300 mg slow-release capsules once daily. The patients were followed up after 4 weeks, when the measurements were repeated. The patients were also evaluated for any side effects related to Theophylline. The pre and post-Theophylline data were compared. The safety profile of Theophylline was assessed by recording side effects related to the drug, any serious side effects, or Theophylline withdrawal.Results: Out of the 109 patients in our study, 96(88%) were males, and 13(12%) were females. Their mean(±SD) age was 69.0±7.8 years(range 46-83 years). After 4 weeks of added Theophylline, there was a statistically significant improvement in FEV1 from 53.3±10.4 to 56.4±10.1 (% predicted mean±SD) (p= 0.03) and FVC from 70.4±10.0 to 73.1±9.8% (p= 0.05). 61% of the patients showed improvement in dyspnoea, with a significant improvement in the MRC score from 3.8±0.8 to 3.2±0.8 (p<0.0001). The patients also showed an increase in saturation from 93.6%±2.3 to 93.8%±2.0, though this was not statistically significant (p= 0.490). 5 patients (5%) had side effects related to Theophylline,though none were serious. The most common side effect was nausea (60%). None of the patients who developed side effects stopped using Theophylline during the study.Conclusion:Theophylline produced a significant increase in the lung function of patients with moderate, severe and very severe COPD and significantly improved their disability caused by dyspnoea, without any serious side effects. Use of Theophylline in stable COPD patients should be weighed however against the risk of possible non-serious side effects, mainly nausea.