Background: In Acute respiratory distress syndrome (ARDS), invasion and activation of pro- and anti-inflammatory mediators and cytokines result in oxidative damage to the lung tissue. Aminophylline is a combination of theophylline and ethyl diamine, has anti-inflammatory, bronchodilator, ROS inhibitor effects, and stimulates surfactant release. Mortality of ARDS in COVID-19 patients is high; aminophylline is expected to reduce the incidence of mortality. Information regarding the use of aminophylline in COVID-19 patients with ARDS is still limited. Objective: To evaluate the efficacy of aminophylline in inflammatory parameters in COVID-19 patients with ARDS. Methods: It was a retrospective cohort observational study at the Universitas Airlangga Hospital. Samples were hospitalised COVID-19 patients with ARDS who received a loading dose of 240-480 mg and a maintenance dose of 720-960 mg aminophylline. The primary outcomes were improved C-reactive protein (CRP), IL-6, lymphocytes, neutrophils, and Neutrophil-lymphocyte ratio (NLR), which were measured before and after administration of aminophylline with a duration of therapy of 1-5 days. Result: A total of 50 patients with ARDS were enrolled in the study. Lymphocyte and CRP decreased (p = 0.002; p = 0.128). IL-6, neutrophil, and NLR increased (p = 0.255; p = 0.064; p = 0.005). Conclusion: It can be concluded that the administration of aminophylline has not improved inflammatory parameters.