Hyper- or hypoventilation are commonly occurring stress responses to arterial puncture around the time of blood sampling and have been shown to rapidly alter arterial blood acid-base parameters. This study aimed to evaluate a physiology-based mathematical method to transform peripheral venous blood acid-base values into mathematically arterialised equivalents following acute, transient changes in ventilation. Data from thirty patients scheduled for elective surgery were analysed using the physiology-based method. These data described ventilator changes simulating 'hyper-' or 'hypoventilation' at arterial puncture and included acid-base status from simultaneously drawn blood samples from arterial and peripheral venous catheters at baseline and following ventilatory change. Venous blood was used to calculate mathematically arterialised equivalents using the physiology-based method; baseline values were analysed using Bland-Altman plots. When compared to baseline, measured arterial and calculated arterialised values at each time point within limits of pH: ± 0.03 and PCO2: ± 0.5 kPa, were considered 'not different from baseline'. Percentage of values considered not different from baseline were calculated at each sampling timepoint following hyper- and hypoventilation. For the physiological method, bias and limits of agreement for pH and PCO2 were -0.001 (-0.022 to 0.020) and -0.02 (-0.37 to 0.33) kPa at baseline, respectively. 60 s following a change in ventilation, 100% of the mathematically arterialised values of pH and PCO2 were not different from baseline, compared to less than 40% of the measured arterial values at the same timepoint. In clinical situations where transient breath-holding or hyperventilation may compromise the accuracy of arterial blood samples, arterialised venous blood is a stable representative of steady state arterial blood.