High-speed trains are operated in increasingly complex railway networks and continual improvement of driver assistance systems is necessary to maintain safety. Speech offers the opportunity to provide information to the driver without disrupting visual attention. However, it is not known whether the transient pressure changes inside trains passing through tunnels interfere with speech intelligibility. Our primary goal was to test whether the most severe pressure variations occurring in high-speed trains (25 hPa in 2 s) affect speech intelligibility in individuals with normal hearing ability and secondly whether a potential effect would depend on the direction of the pressure change. A cross-over design was used to compare speech intelligibility, measured with the monosyllable word test by Wallenberg and Kollmeier, in steady ambient pressure versus subsequent to pressure events, both realised in a pressure chamber. Since data for a power calculation did not exist, we conducted a pilot study with 20 participants to estimate variance of intra-individual differences. The upper 80% confidence limit guided sample size of the main campaign, which was performed with 72 participants to identify a 10% difference while limiting alpha (5%) and beta error (10%). On average, a participant understood 0.7 fewer words following a pressure change event compared to listening in steady ambient pressure. However, this intra-individual differences varied strongly between participants, standard deviation (SD) ± 4.5 words, resulting in a negligible effect size of 0.1 and the Wilcoxon signed rank test (Z = -1.26; p = 0.21) did not distinguish it from chance. When comparing decreasing and increasing pressure events an average of 0.2 fewer words were understood (± 3.9 SD). The most severe pressure changes expected to occur in high-speed trains passing through tunnels do not interfere with speech intelligibility and are in itself not a risk factor for loss of verbal information transmission.