Prolonged breath-hold (BH) represents a valid model for studying the cardiac adaptation to acute hypoxemia in humans. Cardiac magnetic resonance (CMR) allows a 3-dimensional, high resolution, non-invasive and non-ionizing anatomical and functional evaluation of the heart. The aim of the study was to assess the adaptation of the cardiovascular system to prolonged BH in air. Ten male volunteers diving athletes (age 30±6 years) were studied during maximal BH duration with CMR. Four epochs were studied: I, rest; II and III, intermediate BH; and IV, peak BH. Oxygen saturation (O2Sa), heart rate (HR), blood pressure (BP), systemic vascular resistances (VR) and end-diastolic (EDV), end-systolic (ESV) volumes, stroke volume (SV), cardiac output (CO), ejection fraction (EF), maximal elastance index (EL) and systolic wall thickening (SWT) and end-systolic wall stress (ESWS) of left ventricle were measured in all the 4 BH epochs. Average BH duration was 3.7±0.3 min. O2Sa was reduced (I= 97±0.2% range: 96-98%, vs. IV= 84±2%, range: 76-92%; p<0.00001). BP, EDV, ESV, SV, CO and ESWS linearly increased from I to IV epochs, while EF, EL and SWT showed an opposite behavior decreasing from resting to IV (all trends are p<0.01 significant). During prolonged BH in air, a marked enlargement of the LV chamber occurs in healthy diving athletes. This response to acute hypoxemia allows stroke volume, cardiac output and arterial pressure to be maintained in spite of the severe reduction in LV contractile function.