BACKGROUND: Complicated exudative pleural fluid collections have traditionally been treated by either closed tube thoracostomy drainage or open surgical drainage. Complete drainage is important in order to control pleural sepsis, restore pulmonary function, and entrapment. Recently intracavitary fibrinolytic therapy has been advocated as a method to facillitate drainage of complicated exudative pleural effusion and to allow enzymatic debridemant of the restrictive fibrinous sheets covering the pleural surface. The purpose of this study is to prospectively evaluate the effects of image-guided catheter drainage with high dose urokinase(UK) instillation in the treatment of complicated pleural effusions. PATIENTS: Twenty complicated pleural effusion patients that poorly respond to image-guided drainage were allocated to receive UK. There were 8 pneumonia and 12 tuberculosis. METHODS: Drugs were diluted in 250 mL normal saline and were infused intrapleurally through the chest tube or pig-tail catheter in a daily dose of 250,000 IU of UK. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasound and/or computed tomography. RESULTS: The mean UK instillation time was 1.63+/-0.10 The mean volume drained UK instillation was 381.3+/-314.4 mL, and post-UK was 321.6+/-489.5 mL. The follow up duration after UK therapy was mean 212.9+/-194.5 days. We had successful results in 19 cases (95.0%). There were 12 pleural thickenings (60.0%), 2 markedly decreased effusions (10.0%) and 5 cases of no thickening or effusion. In only one patient (5%)with complicated pleural effusion due to tuberculosis, there was recurrence after treatment. CONCLUSIONS: Image-guided drainage with high dose UK instillation (250,000 U/day) in complicated pleural effusion is a safe and more effective method than closed thoracostomy drainage. And this management, in turn, can obviate surgery in most cases.