BACKGROUND: The spectrum of altitude decompression sickness (DCS) is evolving as more cases of atypical pressure fluctuations occur. This ongoing change makes it a difficult condition to diagnose and even more difficult to identify. Both Flight Surgeons and Undersea Medical Officers (UMOs) must keep DCS on the differential. These two cases describe altitude DCS after unique pressure patterns, with one at a markedly lower than expected altitude for DCS.CASE REPORT: Both cases occurred in the F/A-18C and resulted in DCS requiring hyperbaric chamber treatment. The aviator in case 1 experienced an over-pressurization to an unknown depth with a subsequent rapid decompression during a carrier approach at 600 ft (182.9 m) above sea level. The aviator in case 2 experienced cabin pressure fluctuations between 9000 ft (2743.2 m) and 18,000 ft (5486.4 m). Both cases demonstrate the progression of DCS after partial treatment on ground-level oxygen therapy, and the case sequence illustrates how evaluations and protocols changed with experience.DISCUSSION: Decompression sickness is difficult to identify since it does not have a diagnostic test. These cases were even more difficult because of subtle exam findings, reliance on subjective symptoms, and atypical pressure profiles. Environmental, physiological, and psychosocial factors specific to the aviation community can delay the diagnosis and treatment. Descending in altitude and using in-flight emergency oxygen or ground-level oxygen partially treats and masks symptoms for both the aviator and the physician. The Flight Surgeons’ integration within the squadron and collaboration with UMOs is important to identify the first signs of DCS and decrease time to treatment.Lee KJ, Sanou AZ. Decompression sickness in the F/A-18C after atypical cabin pressure fluctuations. Aerosp Med Hum Perform. 2018; 89(5):478–482.