Background: Acute respiratory distress syndrome (ARDS) treatment is based on supportive care such as mechanical ventilation, prophylaxis of stress ulcer, prophylaxis of deep vein thrombosis (DVT), nutritional support, and treatment of underlying disease. Objectives: We aimed to investigate the effects of nebulized heparin on weaning off intubated ARDS patients admitted to the intensive care unit (ICU). Methods: In this double-blind clinical trial study, 60 patients with ARDS receiving routine care according to the ARDS protocol were randomly assigned into two groups: intervention group (receiving nebulized heparin 5000 u/BD for one week) and control group (receiving nebulized sterile water 2 cc/BD for one week). The respiratory index (PaO2/FiO2), pulmonary shunt percentage (measured by ABG), tidal volume, minute ventilation, admission duration in the ICU, and days of mechanical ventilation required were recorded for each patient for one week. Results: There was no significant difference in demographic data between the two groups. Inhaled heparin in patients with ARDS could significantly increase the respiratory index (PaO2/FiO2) and decrease pulmonary shunt percentage, minute ventilation, and tidal volume. It also significantly reduced the number of admission days in the ICU and the need for mechanical ventilation. Conclusions: The result of the present study showed that inhaled heparin in intubated ARDS patients admitted to the ICU improved respiratory and pulmonary status and reduced the need for mechanical ventilation and admission days in the ICU. Nebulizing heparin, as an anti-inflammatory and anti-coagulant agent, is an effective and safe medication for ARDS patients on mechanical ventilation.