BACKGROUND: Gradual ascent is impractical for personnel deploying to the South Pole due to logistical challenges. Prevention of altitude illness relies on prophylactic medications such as acetazolamide and behavioral modifications including hydration and avoidance of overexertion. We present three recent cases of altitude illness that occurred in previously healthy individuals at the South Pole.CASE REPORTS: 1) A 52-yr-old woman not on prophylactics presented with headache and intractable vomiting 7 h after arriving and hiking around the station. She was treated with acetazolamide, dexamethasone, oxygen, and supportive care. Her symptoms resolved during the evacuation flight. 2) A 23-yr-old man presented with dyspnea at rest 3 d after arriving without prophylactic treatments. He had a Sao₂ of 49%, wheezes and crackles on lung exam, and interstitial infiltrates on chest X-ray. His treatment included oxygen, nifedipine, acetazolamide, and dexamethasone. His symptoms resolved during the evacuation flight. 3) A 40-yr-old man presented with dyspnea after a series of strenuous workouts since his arrival 5 d prior. He had a Sao₂ of 41%, and his chest X-ray was consistent with high altitude pulmonary edema. He was treated with oxygen, nifedipine, and fluids before descent to sea level, where his symptoms fully resolved 4 d later.DISCUSSION: These patients illustrate that altitude illness may develop despite medical screening, participant education, and availability of prophylactic medications based on published guidelines. These cases could be attributed to noncompliance and misinformation, bringing to light some of the challenges with managing more diverse populations that deploy to remote environments.Rose JS, Law J, Scheuring R, Ramage MH, McKeith JJ. Serious altitude illness at the South Pole. Aerosp Med Hum Perform. 2020; 91(1):46-50.