Objective:While there is recent interest in using repeated deep inspiratory breath-holds, or prolonged single breath-holds, to improve radiotherapy delivery, breath-holding has risks. There are no published guidelines for monitoring patient safety, and there is little clinical awareness of the pronounced blood pressure rise and the potential for gradual asphyxia that occur during breath-holding. We describe the blood pressure rise during deep inspiratory breath-holding with air and test whether it can be abolished simply by pre-oxygenation and hypocapnia.Methods:We measured blood pressure, oxygen saturation (SpO2) and heart rate in 12 healthy, untrained subjects performing breath-holds.Results:Even for deep inspiratory breath-holds with air, the blood pressure rose progressively (e.g. mean systolic pressure rose from 133 ± 5 to 175 ± 8 mmHg at breakpoint, p < 0.005, and in two subjects, it reached 200 mmHg). Pre-oxygenation and hypocapnia prolonged breath-hold duration and prevented the development of asphyxia but failed to abolish the pressure rise. The pressure rise was not a function of breath-hold duration and was not signalled by any fall in heart rate (remaining at resting levels of 72 ± 2 beats per minute).Conclusion:Colleagues should be aware of the progressive blood pressure rise during deep inspiratory breath-holding that so far is not easily prevented. In breast cancer patients scheduled for breath-holds, we recommend routine screening for heart, cardiovascular, renal and cerebrovascular disease, routine monitoring of patient blood pressure and SpO2 during breath-holding and requesting patients to stop if systolic pressure rises consistently >180 mmHg and or SpO2 falls <94%.Advances in knowledge:There is recent interest in using deep inspiratory breath-holds, or prolonged single breath-holding techniques, to improve radiotherapy delivery. But there appears to be no clinical awareness of the risks to patients from breath-holding. We demonstrate the progressive blood pressure rise during deep inspiratory breath-holds with air, which we show cannot be prevented by the simple expedient of pre-oxygenation and hypocapnia. We propose patient screening and safety guidelines for monitoring both blood pressure and SpO2 during breath-holds and discuss their clinical implications.