The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders.This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living <800 m), assessing cardiac function, including tricuspid regurgitation pressure gradient (TRPG), cardiac index and tricuspid annular plane systolic excursion (TAPSE) by echocardiography combined with heart rate and oxygen saturation measured by pulse oximetry (S_pO2) during submaximal stepwise cycle exercise (10 W increase per 3 min) at their altitude of residence (at 760 m or 3250 m, respectively).52 highlanders (26 females; aged 47.9±10.7 years; body mass index (BMI) 26.7±4.6 kg·m⁻²; heart rate 75±11 beats·min⁻¹;S_pO291±5%;) and 22 lowlanders (eight females; age 42.3±8.0 years; BMI 26.9±4.1 kg·m⁻²; heart rate 68±7 beats·min⁻¹;S_pO296±1%) were studied. Highlanders had a lower restingS_pO2compared to lowlanders but change during exercise was similar between groups (highlandersversuslowlanders −1.4±2.9%versus−0.4±1.1%, respectively, p=0.133). Highlanders had a significantly elevated TRPG and exercise-induced increase was significantly higher (13.6±10.5 mmHgversus6.1±4.8 mmHg, difference 7.5 (2.8 to 12.2) mmHg; p=0.002), whereas cardiac index increase was slightly lower in highlanders (2.02±0.89 L·min⁻¹versus1.78±0.61 L·min⁻¹, difference 0.24 (−0.13 to 0.61) L·min⁻¹; p=0.206) resulting in a significantly steeper pressure–flow ratio (ΔTRPG/Δcardiac index) in highlanders 9.4±11.4 WU and lowlanders 3.0±2.4 WU (difference 6.4 (1.4 to 11.3) WU; p=0.012). Right ventricular-arterial coupling (TAPSE/TRPG) was significantly lower in highlanders but no significant difference in change with exercise in between groups was detected (−0.01 (−0.20 to 0.18); p=0.901).In highlanders, chronic exposure to hypoxia leads to higher pulmonary artery pressure and a steeper pressure–flow relation during exercise.