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Introduction: Over the past several decades, the use of drug therapy in COPD has expanded, and provides an optimistic picture. Methyixanthines are used freely in COPD. Of them, Theophylline is an age old bronchodilator and anti-infammatory agent while Acebrophylline is a newer one. Both are used as add on therapy in management of stable COPD patients on LAMA (long acting muscarinic antagonists like Tiotropium) in present day respiratory practice. This study was designed to compare the efficacy as well as tolerability/side-effects of these two drugs at recommended doses. Materials and Methods: An open randomized comparative longitudinal study was conducted on 40 moderate degree COPD patients over a period of one year. The patients were randomized into Group-1:receiving Acebrophylline 100mg twice daily and Group-2: receiving sustained release (SR) Theophylline 300mg once daily orally, in addition to 18μgm Tiotropium inhalation per day through metered dose inhaler. Spirometric variables, symptomatic benefit and adverse effects were recorded on three visits (day '0', '21' and '42'). All the data were analyzed by SPSS version 17. Results: A comparable clinical improvement of symptoms score and spirometric parameters with both the drugs has been observed (p-value>0.05). Amount of sputum, frequency of use of reliever medication and dyspnoea showed improvement with both the drugs but cardiovascular side effects are less with Acebrophylline. Conclusion: This study reaffirms the rationale of use of Methylxanthines as add on therapy with LAMA in COPD management and cardiac safety level with Acebrophylline was considerable. [ABSTRACT FROM AUTHOR]