U-2 pilots are at an increased risk of decompression sickness compared with other aviators in the U.S. Air Force. This is due to the extreme altitudes at which the missions take place. Presented here is a case of decompression sickness that occurred in a U-2 pilot who was wearing a full-pressure suit while flying at an altitude greater than 70,000 ft, with a pressurized cabin altitude of 29,200 ft. This case demonstrates the continued need for pilot education and awareness of DCS risk factors and symptoms.