The recommended treatment for exertional heat stroke is immediate, whole-body immersion in < 10 °C water until rectal temperature (Tre) reaches ≤ 38.6°C. However, real-time Tre assessment is not always feasible or available in field settings or emergency situations. We defined and validated immersion durations for water temperatures of 2-26°C for treating exertional heat stroke. We compiled data for 54 men and 18 women from 7 previous laboratory studies and derived immersion durations for reaching 38.6°C Tre. The resulting immersion durations were validated against the durations of cold-water immersion used to treat 162 (98 men; 64 women) exertional heat stroke cases at the Falmouth Road Race between 1984 and 2011. Age, height, weight, body surface area, body fat, fat mass, lean body mass, and peak oxygen uptake were weakly associated with the cooling time to a safe Tre of 38.6°C during immersions to 2-26°C water (R2 range: 0.00-0.16). Using a specificity criterion of 0.9, receiver operating characteristics curve analysis showed that exertional heat stroke patients must be immersed for 11-12min when water temperature is ≤ 9°C, and for 18-19min when water temperature is 10-26°C (Cohen's Kappa: 0.32-0.75, p < 0.001; diagnostic odds ratio: 8.63-103.27). The reported immersion durations are effective for > 90% of exertional heat stroke patients with pre-immersion Tre of 39.5-42.8°C. When available, real-time Tre monitoring is the standard of care to accurately diagnose and treat exertional heat stroke, avoiding adverse health outcomes associated with under- or over-cooling, and for implementing cool-first transport second exertional heat stroke policies.