The standard palliation of malignant pleural effusions involves tube thoracostomy drainage with chemical pleurodesis. The insufflation of intrapleural talc under thoracoscopic guidance (n = 39) was evaluated against documented controls that consisted of patients (n = 85) who participated in a randomized study with tube thoracostomy drainage followed by either bleomycin or tetracycline sclerosis. Under local anesthesia, which was supplemented by intravenous sedation, patients in the talc group underwent complete pleural fluid evacuation. The talc was then insufflated evenly on the entire pleural surface under thoracoscopic guidance. Of the patients in the talc group who survived their disease process, 97% had a successful pleurodesis at 30 days and 95% at 90 days. In comparison, the bleomycin group demonstrated a success rate of 64% at 30 days and 70% at 90 days (p = 0.003 and p = 0.047 versus the talc group). The tetracycline group had successful pleurodesis in only 33% at 30 days and 47% at 90 days (p < 0.001 and p < 0.001 versus the talc group). There were only two patients in the talc group in whom pleurodesis was not successful, and both were subsequently found to have extraluminal compression of the right lower lobe bronchus, which prevented lung reexpansion. These data demonstrate that the insufflation of talc into the pleural cavity under thoracoscopic guidance is a safe and efficacious procedure in the control of malignant pleural effusions.