Background: Bronchial asthma is a non-communicable disease that is highly prevalent globally, and the incidences of this drug increase daily with the increased environmental pollution. The most common interventional treatment for asthma includes methylxanthines, mainly doxofylline and aminophylline (ethylenediamine salt of theophylline). This study compared the efficacy of these two methylxanthines in treating bronchial asthma. Methodology: A literature search was performed through PubMed, MEDLINE, Google Scholar, and Cochrane. The Cochrane RevMan 5.4 software was used to perform a meta-analysis for the included studies.Results: Ten studies were included based on the satisfaction of the eligibility criteria. From the analysis, the spirometric values of FEV1, PEFR, FVC, and FEV/FVC demonstrated a statistically significant change/improvement from the baseline when using both aminophylline and doxofylline in the treatment of bronchial asthma. There was significant difference in mean FEV1 and FVC between the two drugs of (MD -0.02, 95% CI -0.03 to -0.01; P = 0.01) and (MD 0.02, 95% CI 0.01 to 0.04; P = 0.009), respectively. However, FEV1/FVC was not significant between aminophylline and doxofylline (MD 0.15, 95% CI -0.34 to 0.64; P = 0.55). Safety assessment between the two drugs shows significant differences with the use of both aminophylline and doxofylline OR 2.26, 95% CI 1.72 to 2.98; P < 0.00001). The heterogeneity across different analyses was high.Conclusion: The current study concluded that both doxofylline and aminophylline significantly improved the baseline conditions and functions of the lungs during the treatment of bronchial asthma. Doxofylline was superior to aminophylline in its efficacy and was also associated with lower incidences of adverse events and complications compared to aminophylline.