The incidence of an acute compartment syndrome (ACS) of the thigh is less than 1%. It is most common in the setting of muscle overuse or muscle injury, as well as secondary to trauma, such as a femoral fracture. We present a case of an ACS in a young, healthy, and semiprofessional athlete with normal coagulation who sustained an acute stress fracture of the distal femur. After the initial fracture osteosynthesis, the patient suffered from a compartment syndrome in the right anterior aspect of the distal thigh. Following rapid surgical fasciotomy, the case was uneventful, and he returned to his preinjury sport level without any neurological consequences. This case confirms that ACS in the thigh is rare, but mainly occurs in young males with a large muscle mass due to participation in various athletic programs. We hypothesize that constant muscle over-usage primes for a larger amount of contused and protruding muscle mass in the small femoral compartment. Hence, the fatigued muscle subjects the bone to an increased mechanical force resulting in an overloading process. This ensues the accumulation of femoral microfractures and primes for the occurrence of an increased rate of stress fractures and an ACS in the thigh.