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Noise exposure is affecting health-related quality of life (HRQoL). There are many modelling approaches linking specific noise sources with single health-related outcomes. However, an integrated approach is missing taking into account measured levels as well as noise annoyance and sensitivity and assessing their independent association with HRQoL domains. Therefore, we investigated the predictive association of most common transportation noise sources (aircraft, railway and road traffic) as well as transportation noise annoyance and noise sensitivity with HRQoL using data from SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We assessed 2035 subjects, who participated in the second and third wave of SAPALDIA (3&4) and had complete information on exposure, outcome and covariates. At SAPALDIA3, we calculated annual means (Lden) of source-specific transportation noise exposure at the most exposed facade of participant's dwelling floor height. Participants reported noise annoyance on the widely used 11-point ICBEN scale and answered to 10 questions assessing individual noise sensitivity. To assess the potentially predictive effect of these noise exposures, HRQoL was assessed about 8 years later (SAPALDIA4) using the SF-36. We performed predictive multiple quantile regression models to elucidate associations of noise parameters measured at SAPALDIA3 with median SF-36 scores at SAPALDIA4. Source-specific transportation noise exposures showed few yet not consistent associations with HRQoL scores. We observed statistically significant negative associations of transportation noise annoyance with HRQoL scores covering mental health components (adjusted difference in SF-36 mental health score between highest vs. lowest annoyance tertile: -2.54 (95%CI: -3.89; -1.20). Noise sensitivity showed strongest and most consistent associations with HRQoL scores covering both general and mental health components (adjusted difference in SF-36 scores between highest vs. lowest sensitivity tertile: Mental health -5.96 (-7.57; -4.36); general health -5.16 (-7.08; -3.24)). Within all noise parameters, we predominantly observed negative associations of noise sensitivity with HRQoL attaining a magnitude of potential clinical relevance. This implies that factors other than transportation noise exposure may be relevant for this exposure-outcome relation. Nonetheless, transportation noise annoyance showed relevant associations with mental health components, indicating a negative association of transportation noise with HRQoL., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)