Background: Chemical pleurodesis is an important tool in the management of refractory pleural effusion. Although talc is widely used as a sclerosing agent of choice, alternative agents like doxycycline have emerged as cheaper and safer agents for chemical pleurodesis. Objective: The aim was to evaluate the effectiveness and clinical outcomes of chemical pleurodesis using doxycycline (500 mg single dose) in the treatment of malignant and nonmalignant pleural effusion and recurrent pneumothorax. Materials and methods: A total of 36 patients, of which 23 patients with malignant pleural effusion, nine patients with pneumothorax, and four patients with nonmalignant effusion, were included in the analysis. After intercostal drainage (ICD) of air or fluid, xylocaine was instilled for pleural anesthesia, and 500 mg of doxycycline was used as a sclerosant. Successful pleurodesis was defined as expanded lung with close approximation between visceral and parietal pleura and minimal to no effusion or pneumothorax at 2 weeks. Results: At the end of 2 weeks, all 23 patients with malignant pleural effusion and nine patients with refractory pneumothorax had successful pleurodesis, but four patients with hepatic hydrothorax had no response. The most common adverse events with pleurodesis included chest pain and fever. Conclusion and clinical significance: Doxycycline was found to be a safe and effective agent for chemical pleurodesis in patients with malignant pleural effusions and recurrent pneumothorax. However, the outcome of hepatic hydrothorax remained unsatisfactory.