Heat-related illness and mortality increase significantly during heatwaves. Out-of-hospital treatment to avoid elevation of body core temperature (hyperthermia) could be beneficial for selected patients. Negative pressure devices have been proposed as an effective treatment method. This study compared the effects of two devices on healthy volunteers under continuous passive heat stress in a climatic chamber. Nine subjects were studied in a prospective cross-over study on two separate days. Subjects were randomized to treatment with either CoreControl® (CC) or ThermoTube (TT) on the first day. They were exposed to an ambient temperature above skin temperature and high air humidity throughout the experiment. Treatment intended to prevent the development of hyperthermia started after 60 min of passive warming. Core temperature continued to rise during treatment with CC, whereas it dropped slightly and then stabilized during treatment with TT.