Periodic breathing (PB) affects sleep at high altitude, with differences between males and females as we showed previously. Our aim was to explore cardio-respiratory adaptations to high altitude in trained professional climbers (CL) as compared to male and female non-climbers (NC). In 45 healthy subjects (23 male NC, 14 female NC and 8 male CL) participating in the HIGHCARE project, we performed an overnight polisomnography with the wearable MAGIC system and the portable Embletta polisomnographic device: at sea level (SL); within 48-h after arrival at 3500m; within 48-h and 12 days after arrival at Mt.Everest Base Camp (5400m). Arterial pressure (Portapres) was also monitored in supine position for 10 minutes during daytime. In all subjects, mean arterial pressure increased from SL (77 ± 3 mmHg, M ± SEM) to 3500m (82 ± 2) and 5400m (89 ± 2 and 86 ± 2, acute and prolonged-exposure) and pulse interval decreased from SL (1074 ± 30 ms) to 3500m (896 ± 25) and to acute-exposure to 5400 m (851 ± 24), without significant differences between CL, male and female NC. However, during prolonged-exposure, pulse interval was significantly shorter in NC (806 ± 26) than in CL (950 ± 43, p < 5%). At 3500m, apnea-hypopnea index (AHI) was significantly higher in male (40 ± 33) than in female NC (2.4 ± 2.8) or CL (6.5 ± 5), due to central apneas. At 5400m (acute), AHI was significantly higher in male NC (87.5 ± 35) and CL (78 ± 38) than in female NC (41 ± 43). After 12 days at 5400m, AHI was significantly higher in male NC (97 ± 30) only, without significant differences between CL (73 ± 23) and female NC (44 ± 39). In conclusion, acclimatization differs in CL and NC. At 3500m, PB affects male NC only, while under acute exposure at 5400m it affects both male NC and CL. Under prolonged exposure to 5400m climbers display a better cardiorespiratory performance than NC, suggesting that training facilitates cardiac and respiratory adaptations to high-altitude hypoxia. [unrestricted support by Boehringer Ingelheim, Germany; Banca Intesa San Paolo, Italy and Sapio Life srl, Italy]