Intake of paracetamol has been associated with development of asthma. The aim of this study was to address a possible association between intake of paracetamol and risk of adult-onset asthma. Using a multidisciplinary postal questionnaire survey concerning health and lifestyle we prospectively studied 19,349 adult twins enrolled in the nationwide Danish Twin Registry. There was a higher prevalence of new-onset asthma in subjects who reported frequent intake of paracetamol at baseline compared with subjects without this determinant (12.0% vs. 4.3%), OR = 3.03 (1.51-6.11), p = 0.005. The result remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema, and intake of medications other than paracetamol, OR = 2.16 (1.03-4.53), p = 0.041. Frequent intake of paracetamol is an independent risk factor for adult-onset asthma.