The effects of creatine (Cr) supplementation on cardiovascular, metabolic, and thermoregulatory responses, and on the capacity of trained humans to perform prolonged exercise in the heat was examined. Endurance-trained males (n = 21) performed 2 constant-load exercise tests to exhaustion at 63 ± 5 % VO2max in the heat (ambient temperature: 30.3 ± 0.5 °C) before and after 7 d of Cr (20 g · d–1 ’ Cr + 140 g • d–1 glucose polymer) or placebo. Cr increased intraccl-lular water and reduced thermoregulatory and cardiovascular responses (e.g., heart rate, rectal temperature, sweat rate) but did not significantly increase time to exhaustion (47.0 ± 4.7 min vs. 49.7 ± 7.5 min, P = 0.095). Time to exhaustion was increased significantly in subjects whose estimated intramuscular Cr levels were substantially increased (“responders”: 47.3 ± 4.9 min vs. 51.7 ± 7.4 min, P = 0.031). Cr-induced hyperhydration can result in a more efficient thermoregulatory response during prolonged exercise in the heat.