BACKGROUND: Little is known about the relation between regular use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of asthma at the population level. The aim of this study was to examine a possible association between intake of NSAIDs and risk of adult-onset asthma. METHODS: Using data from two multidisciplinary postal questionnaire surveys concerning health and lifestyle, we prospectively studied 19 349 adult twins enrolled in the nationwide Danish Twin Registry. RESULTS: We found a higher prevalence of new-onset asthma in subjects who used NSAIDs (other than aspirin) regularly compared with non-users (7.7% vs 4.3%), OR = 1.87 (1.25-2.81), P = 0.002. The result remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema and intake of medications other than NSAIDs, OR = 1.90 (1.26-2.85), P = 0.002. CONCLUSIONS: Regular use of NSAIDs other than aspirin may be a risk factor for adult-onset asthma. This observation must be accommodated in explanations of the relationship between use of analgesics and risk of asthma.