Background: Few studies have considered aircraft noise annoyance and noise sensitivity in analyses of the health effects of aircraft noise, especially in relation to medication use. This study aims to investigate the moderating and mediating role of these two factors in the relationship between aircraft noise levels and medication use among 5860 residents of ten European airports included in the HYENA and DEBATS studies. Methods: Information on aircraft noise annoyance, noise sensitivity, medication use, and demographic, socioeconomic and lifestyle factors was collected during a face-to-face interview at home. Medication was coded according to the Anatomical Therapeutic Chemical (ATC) classification. Outdoor aircraft noise exposure was estimated by linking the participant's home address to noise contours using Geographical Information Systems (GIS) methods. Logistic regressions with adjustment for potential confounding factors were used. In addition, Baron and Kenny's recommendations were followed to investigate the moderating and mediating effects of aircraft noise annoyance and noise sensitivity. Results: A significant association was found between aircraft noise levels at night and antihypertensive medication only in the UK (OR = 1.43, 95%CI 1.19-1.73 for a 10 dB(A)-increase in Lnight). No association was found with other medications. Aircraft noise annoyance was significantly associated with the use of antihypertensive medication (OR = 1.33, 95%CI 1.14-1.56), anxiolytics (OR = 1.48, 95%CI 1.08-2.05), hypnotics and sedatives (OR = 1.60, 95%CI 1.07-2.39), and antasthmatics (OR = 1.44, 95%CI 1.07-1.96), with no difference between countries. Noise sensitivity was significantly associated with almost all medications, with the exception of the use of antasthmatics, showing an increase in ORs with the level of noise sensitivity, with differences in ORs among countries only for the use ofantihypertensive medication. The results also suggested a mediating role of aircraft noise annoyance and a modifying role of both aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and medication use.Conclusions: The present study is consistent with the results of the small number of studies available to date suggesting that both aircraft noise annoyance and noise sensitivity should be taken into account in analyses of the health effects of exposure to aircraft noise.