Schulze, A, Laessing, J, Kwast, S, and Busse, M. Influence of a vented mouthguard on physiological responses in handball. J Strength Cond Res 34(7): 2055-2061, 2020-Mouthguards (MGs) improve sports safety. However, airway obstruction and a resulting decrease in performance are theoretical disadvantages regarding their use. The study aim was to assess possible limitations of a "vented" MG on aerobic performance in handball. The physiological effects were investigated in 14 male professional players in a newly developed handball-specific course. The measured values were oxygen uptake, ventilation, heart rate, and lactate. Similar oxygen uptake (V[Combining Dot Above]O2) values were observed with and without MG use (51.9 ± 6.4 L·min·kg vs. 52.1 ± 10.9 L·min·kg). During maximum load, ventilation was markedly lower with the vented MG (153.1 ± 25 L·min vs. 166.3 ± 20.8 L·min). The endexpiratory concentrations of O2 (17.2 ± 0.5% vs. 17.6 ± 0.8%) and CO2 (4.0 ± 0.5% vs. 3.7 ± 0.6%) were significantly lower and higher, respectively, when using the MG. The inspiration and expiration times with and without the MG were 0.6 ± 0.1 seconds vs. 0.6 ± 0.1 seconds and 0.7 ± 0.2 seconds vs. 0.6 ± 0.2 seconds (all not significant), respectively, indicating that there was no relevant airflow restriction. The maximum load was not significantly affected by the MG. The lower ventilation for given V[Combining Dot Above]O2 values associated with MG use may be an effect of improved biomechanics and lower respiratory drive of the peripheral musculature.