Pleural fluid loculations due to complicated parapneumonic effusion (CPE), empyema, tubercular effusion and traumatic hemothorax can be managed either by video-assisted thoracoscopic surgery (VATS) or intrapleural ibrinolytic therapy (IPFT). The former is more invasive, not easily available and is also more expensive. On the other hand, IPFT is less invasive, cheaper, easily accessible and if used early, in loculated pleural collections, break loculations and early pleural peel, thereby facilitating pleural space drainage.To study the efficacy of IPFT in facilitating pleural space drainage in loculated pleural collections of diverse aetiologies.A five-year retrospective, observational study of 200 patients, with loculated pleural collections and failed tube drainage and managed with IPFT was carried out. Responders were defined as those with significant volume of fluid drained and significant radiological resolution.There were 106 (53%) cases of CPE, 59 (29.5%) cases of tubercular effusion, 23 (11.5%) cases of empyema and 12 (6%) cases of hemothorax. Responders were 148 (74%) in number. The distribution of responders as per type of loculated pleural collection was as follows: CPE 88 (83%), tubercular 37 (62.7%), empyema 14 (60.8%) and traumatic hemothorax 11 (91.6%). The adverse effects were mild and included chest pain in six patients and low-grade transient fewer in three cases.Intrapleural fibrinolytic therapy is a safe and cost-effective option in the management of selected patients with loculated pleural effusions.