STUDY OBJECTIVES: To analyze and compare radiologic lung expansion after talc pleurodesis performed either by videothoracoscopy or chest tube and correlate it with clinical outcome. Secondary end points evaluated were as follows: clinical efficacy; quality of life; safety; and survival. METHODS: Prospective randomized study that included 60 patients (45 women, 15 men; mean age, 55.2 years) with recurrent malignant pleural effusion between January 2005 and January 2008. They were randomized into the following two groups: video-assisted thoracic surgery (VATS) talc poudrage; and talc slurry (TS) administered through a chest tube. Lung expansion was evaluated through chest CT scans obtained 0, 1, 3 and 6 months after pleurodesis. Complications, drainage time, hospital stay, and quality of life (Medical Outcomes Study 36-item short form and World Health Organization quality-of-life questionnaires) were also analyzed. RESULTS: There were no significant differences in preprocedure clinical and pathologic variables between groups. The immediate total (ie, > 90%) lung expansion was observed in 27 patients (45%) and was more frequent in the VATS group (60% vs 30%, respectively; p = 0.027). During follow-up, 71% of the patients showed unaltered or improved lung expansion and 9 patients (15%) needed new pleural procedures (VATS group, 5 recurrences; TS group, 4 recurrences; p = 0.999). No differences were found between groups regarding quality of life, complications, drainage time, hospital stay, and survival. Immediate lung expansion did not correlate with radiologic recurrence, clinical recurrence, or complications (p = 0.60, 0.15, and 0.20, respectively). CONCLUSION: Immediate partial lung expansion was a frequent finding and was more frequent after TS. Nonetheless, no correlation between immediate lung expansion and clinical outcome was found in this study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NTC00789087.