A series of human field studies demonstrated that simulated nocturnal traffic noise exposure impaired sleep quality and endothelial function, which could be significantly improved after intake of vitamin C in case of endothelial function. However, it remains unclear whether these changes follow a sex-specific pattern. Thus, we aimed to analyze the effect of simulated nocturnal train noise exposure on sleep quality, endothelial function and its associated changes after vitamin C intake, and other hemodynamic and biochemical parameters in young healthy men and women. We used data from a randomized crossover study, wherein 70 healthy volunteers (50% women) were each exposed to one control pattern (regular background noise) and two different train noise scenarios (30 or 60 train noise events per night, with average sound pressure levels of 52 and 54 dB(A), respectively, and peak sound level of 73-75 dB(A)) in their homes for three nights. After each night, participants visited the study center for the measurement of endothelial function as well as other hemodynamic and biochemical parameters. Sleep quality measured via self-report was significantly impaired after noise 30 and noise 60 nights in both men and women ( < 0.001 vs. control). Likewise, endothelial function measured by flow-mediated dilation (FMD) was significantly impaired after noise 30 and noise 60 nights in both men and women ( < 0.001 vs. control). While in women, vitamin C intake significantly improved FMD after both noise 30 and noise 60 study nights compared to control nights, no significant changes were observed in men. Exposure to simulated nocturnal train noise impairs sleep quality and endothelial function in both men and women, whereas a significant improvement of endothelial function after noise exposure and vitamin C intake could only be observed in women. These findings suggest for the first time that in men other mechanisms such as oxidative stress causing endothelial dysfunction may come into play.