Extreme heat events and consequent detrimental heat-health outcomes have been increasing in recent decades and are expected to continue with future climate warming. While many indices have been created to quantify the combined atmospheric contributions to heat, few have been validated to determine how index-defined heat conditions impact human health. However, this subset of indices is likely not valid for all situations and populations nor easily understood and interpreted by health officials and the public. In this study, we compare the ability of thresholds determined from the National Weather Service’s (NWS) Heat Index (HI), the Wet Bulb Globe Temperature (WBGT), and the Universal Thermal Climate Index (UTCI) to predict the compensability of human heat stress (upper limits of heat balance) measured as part of the Pennsylvania State University’s Heat Environmental Age Thresholds (PSU HEAT) project. While the WBGT performed the best of the three indices for both minimal activities of daily living (MinAct; 83 W·m⁻²) and light ambulation (LightAmb; 133 W·m⁻²) in a cohort of young, healthy subjects, HI was likewise accurate in predicting heat stress compensability in MinAct conditions. HI was significantly correlated with subjects’ perception of temperature and humidity as well as their body core temperature, linking perception of the ambient environment with physiological responses in MinAct conditions. Given the familiarity the public has with HI, it may be better utilized in the expansion of safeguard policies and the issuance of heat warnings during extreme heat events, especially when access to engineered cooling strategies is unavailable.