Background/aims Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude. Methods This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV 1 ) 40–80% pred, oxygen saturation measured by pulse oximetry ( S pO 2 ) ≥92% and arterial carbon dioxide tension ( P aCO 2 ) <6 kPa. Patients underwent baseline evaluation and HAST, breathing normobaric hypoxic air (inspiratory oxygen fraction ( F IO 2 ) of 15%) for 15 min, at low altitude (760 m). Cut-off values for a positive HAST were set according to British Thoracic Society (BTS) guidelines (arterial oxygen tension ( P aO 2 ) <6.6 kPa and/or S pO 2 <85%). The following day, patients travelled to HA (3100 m) for two overnight stays where ARAHE development including acute mountain sickness (AMS), Lake Louise Score ≥4 and/or AMS score ≥0.7, severe hypoxaemia ( S pO 2 <80% for >30 min or 75% for >15 min) or intercurrent illness was observed. Results ARAHE occurred in 50 (66%) patients and 23 out of 75 (31%) were positive on HAST according to S pO 2 , and 11 out of 64 (17%) according to P aO 2 . For S pO 2 / P aO 2 we report a sensitivity of 46/25%, specificity of 84/95%, positive predictive value of 85/92% and negative predictive value of 44/37%. Conclusion In COPD patients ascending to HA, ARAHE are common. Despite an acceptable positive predictive value of the HAST to predict ARAHE, its clinical use is limited by its insufficient sensitivity and overall accuracy. Counselling COPD patients before altitude travel remains challenging and best focuses on early recognition and treatment of ARAHE with oxygen and descent.