A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether non-steroidal anti-inflammatory drugs (NSAIDs) decrease the effect of pleurodesis. Only 17 papers were identified using the search below. Three papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that despite a limited number and type of study, there is some histopathological evidence to support the concern that NSAIDs may reduce effectiveness of pleurodesis. Until further clinical studies with appropriate outcome measures are available, NSAIDs following pleurodesis should be used with caution and probably avoided routinely.