Purpose. Isometric exercise (IE) training has been shown to be effective at reducing resting blood pressure (BP). However, there is a lack of clarity as to which IE modality is more effective at reducing resting BP. Acute responses following a single session of IE have been shown to predict long-term training adaptions. It was hypothesised that when using a comparative workload, exercises that recruit more muscle mass have a greater proclivity to induce transient reductions in BP than those that use smaller amounts of muscle mass. To test this hypothesis, the current study set out to compare the acute haemodynamic and autonomic responses following a single session of isometric wall squat (IWS) and isometric handgrip (IHG). Method. Twenty-six sedentary participants performed a single IWS and IHG session comprised of 4 x 2-min contractions, with 2-min rest, at 95 HRpeak and 30% MVC, respectively. Total power spectral density of HR variability and associated low-frequency and high-frequency power spectral components were recorded in absolute and normalized units before, during, and 10-min and 1hour after each IE session. Heart rate (HR) was recorded via electrocardiography and baroreceptor reflex sensitivity via the sequence method. Continuous BP was recorded via the vascular unloading technique and stroke volume and cardiac output (Q̇) via impedance cardiography. Total peripheral resistance (TPR) was calculated according to Ohm’s law. The change from baseline for each variable was used for comparative analysis. Results. During IE, there was a significantly greater increase in systolic BP, diastolic BP, mean BP, HR and Q̇ in the IWS condition (all P= <0.001). There was also significantly less TPR during IWS exercise (P= 0.006). During the 10-min recovery window, there was a significantly greater reduction in systolic BP, diastolic BP, mean BP (all P= 0.005) and TPR (P= <0.001). There were no differences in any autonomic variables during recovery, and no differences in any variables 1-hour post exercise. Conclusion. Isometric wall squat exercise produces a greater cardiovascular response during exercise, with a greater reduction in BP and TPR during a 10-min recovery period. These acute responses may be mechanistically linked to the chronic reductions in resting BP reported after IE training interventions