A 38-year-old Asian male with severe mitral valve regurgitation underwent elective minimally invasive mitral valve repair with artificial chordae and concomitant Cox-Maze procedure. Cardiopulmonary bypass required large peripheral cannulas due to the patient's increased body surface area with a total bypass time of 216 min. At 10 h, the patient reported progressive right lower extremity pain with evidence of swelling, diffuse paresthesias, and weak peripheral pulses. The patient underwent double-incision lower leg fasciotomies, revealing significant interstitial fluid and bulging muscle chambers. Compartment syndrome demonstrates non-traumatic etiologies. Elevated body mass index, Kawashima Type D femoral artery classification, prolonged bypass times, driven partially due to concomitant Cox-Maze, and larger cannula sizes should increase the index of suspicion.