Background: Malignant pleural effusions (MPEs) can occur due to practically any type of cancer. MPEs frequently impair quality of life. There are numerous techniques for managing MPEs; each drains the pleural space and relieves respiratory symptoms. Pleurodesis is described as the formation of a symphysis between two layers of pleura to avoid the recurrence of effusions. Numerous chemical compounds are being investigated for use in pleurodesis. The purpose of this research was to examine the medical pleurodesis results performed with three different chemical agents in order to determine the most effective one with the fewest side effects. Methods: This study enrolled 60 patients from the Medical Oncology department at Zagazig University Hospitals, Egypt between January 2021 and January 2022. All patients were with MPEs. We enlisted 60 patients, separated them into three groups of 20 each, and had them undergo medical pleurodesis with three different chemical agents in comparison: povidone-iodine, doxycycline, and bleomycin. Sex, age, side of the effusion, treatment outcome (success and failure), and adverse effects were analyzed. Results: After pleurodesis, findings were evaluated, and the final success rates were 80% for povidone-iodine, 75% for bleomycin, and 65% for doxycycline. Conclusions: When utilized appropriately, povidone-iodine, doxycycline, and bleomycin are practically similarly efficient and safe sclerosing agents. While the povidone-iodine and doxycycline are similarly efficient and secure as bleomycin as chemical agents for pleurodesis in cases of MPEs, they are less costly and more commonly available.