Acute compartment syndrome is a life-threatening complication in trauma patients. Not only regional neuromuscular disability, but also systemic organ disorders can result from prolonged tissue ischemia. In this report, we describe 2 cases of acute atraumatic compartment syndrome complicated with severe heat stroke. In both cases, emergency fasciotomy was rapidly performed after recognition of the syndrome, but serious regional neuromuscular disabilities remained. Microvascular endothelial injury is an important mechanism of acute atraumatic compartment syndrome. Thrombi diffusely formed in the compartmental space hinder establishment of reperfusion even after fasciotomy. Furthermore, disruption of fibrinolysis due to heat stroke could enhance this damage.