The safety of talc pleurodesis is under dispute following reports of talc-induced acute respiratory distress syndrome (ARDS) and death. We investigated the safety of large-particle talc for thoracoscopic pleurodesis to prevent recurrence of primary spontaneous pneumothorax (PSP). 418 patients with recurrent PSP were enrolled between 2002 and 2008 in nine centres in Europe and South Africa. The main exclusion criteria were infection, heart disease and coagulation disorders. Serious adverse events (ARDS, death or other) were recorded up to 30 days after the procedure. Oxygen saturation, supplemental oxygen use and temperature were recorded daily at baseline and after thoracoscopic pleurodesis (2 g graded talc). During the 30-day observation period following talc poudrage, no ARDS (95% CI 0.0-0.9%), intensive care unit admission or death were recorded. Seven patients presented with minor complications (1.7%, 95% CI 0.7-3.4%). After pleurodesis, mean body temperature increased by 0.41°C (95% CI 0.33-0.48°C; p<0.001) at day 1 and returned to baseline value at day 5. Pleural drains were removed after day 4 in 80% of patients. Serious adverse events, including ARDS or death, did not occur in this large, multicentre cohort. Thoracoscopic talc poudrage using larger particle talc to prevent recurrence of PSPS can be considered safe.