Background: There is epidemiological evidence that the use of acetaminophen may increase the risk of developing asthma. Objectives: To investigate the risk of asthma and other allergic disorders associated with the current use of acetaminophen in 13 to 14 year old children in different populations worldwide. Methods: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, 13 to 14 year old children completed written and video questionnaires, obtaining data on current symptoms of asthma, rhinoconjunctivitis and eczema, and a written environmental questionnaire obtaining data on putative risk factors including acetaminophen use in the past 12 months. The primary outcome measure was the odds ratio (OR) of current asthma symptoms associated with acetaminophen use calculated by logistic regression. Results: A total of 322,959 adolescent children from 113 centres in 50 countries participated. In the multivariate analyses the recent use of acetaminophen was associated with an exposure-dependent increased risk of current asthma symptoms [OR 1.43 (95% CI 1.33 to 1.53) and 2.51 (95% CI 2.33 to 2.70) for medium and high versus no use respectively]. Acetaminophen use was also associated with an exposure-dependent increased risk of current symptoms of rhinoconjunctivitis and eczema. Conclusions: Acetaminophen use may represent an important risk factor for the development and/or maintenance of asthma, rhinoconjunctivitis and eczema in adolescent children.