Transportation noise is a growing public health concern worldwide and epidemiological evidence has linked road traffic noise with mortality. However, incongruent effect estimates have been reported between incidence and mortality studies.Therefore, the present study aimed to investigate whether long-term exposure to residential road traffic noise at the most and least exposed façades was associated with all-cause, cardiovascular disease (CVD), ischemic heart disease (IHD), stroke, respiratory, or cancer mortality in a Danish cohort study.In a cohort of 52,758 individuals from Copenhagen and Aarhus, we estimated road traffic noise at the most and least exposed façades, as well as ambient air pollution, at all present and historical residential addresses from 1987 to 2016. Using the Danish cause of death register we identified cause-specific mortality. Analyses were conducted using Cox proportional hazards models.Ten-year time-weighted mean road traffic noise exposure at the most exposed façade was associated with an 8% higher risk for all-cause mortality per interquartile range (IQR; 10.4 dB) higher exposure level (95% CI: 1.05–1.11). Higher risks were also observed for CVD (HR = 1.13, 95% CI: 1.06–1.19) and stroke (HR = 1.11, 95% CI: 0.99–1.25) mortality. Road traffic noise at the least exposed façade (per IQR; 8.4 dB) was associated with CVD (HR = 1.09, 95% CI: 1.03–1.15), IHD (HR = 1.10, 95% CI: 1.01–1.21) and stroke (HR = 1.06, 95% CI: 0.95–1.19) mortality. Results were robust to adjustment for PM2.5 and NO2.In conclusion, this study adds to the body of evidence linking exposure to road traffic noise with higher risk of mortality.