To evaluate the clinical safety, efficacy, and cost of a small indwelling pleural catheter (7F, Turkel Safety Thoracentesis System [Sherwood, Davis, and Geck; St. Louis]) vs repeated needle thoracentesis or closed tube thoracostomy as a means to drain a large-volume pleural effusion. Inpatients in a tertiary care university teaching hospital in urban Chicago. Prospective, consecutive patient comparative study using historical controls. Fifty-seven therapeutic aspirations in 23 patients with large pleural effusions as defined by opacification of at least one third of the hemithorax on chest radiography. Patients were excluded if they had a history of thoracic surgery, documented loculations, structural chest abnormalities, severe coagulopathy, or refused to give informed consent. Volume of each pleural aspiration, total fluid removed, pleural fluid lactate dehydrogenase, protein, glucose, cytologic analysis, microbiologic stains, and cultures based on clinical indications. We found that initial thoracentesis and repeated pleural drainage using the indwelling catheter system is a safe, efficacious, and cost-effective procedure that may aid the evacuation and management of a large-volume pleural effusion. There were fewer adverse effects and complications such as pneumothorax, splenic laceration, hemopneumothorax, local pain, dry tap, and hematomas, as compared with previous reports. The overall complication rate was 12% (7/57). There were two pneumothoraces detected (3.5%), one of which required closed tube thoracostomy for treatment (1.75%). A further benefit comes in the form of a significant cost savings at our institution ($80 vs $240) when this needle-catheter system is used in place of closed tube thoracostomy in the drainage of a large-volume pleural effusion. An indwelling pleural catheter with the Turkel safety needle-catheter (as described in the study) can be used to successfully drain the pleural space with reduced morbidity and a significant cost saving in comparison to repeated needle thoracenteses or closed tube thoracostomy.