Isolated systolic hypertension (ISH) is the most common form of hypertension in older people. It is characterized by increased resting systolic blood pressure (sBP) and increased sBP in response to exercise. It has previously been shown that slow breathing training reduces resting sBP, and the objective of the present study was to determine whether it also reduced the blood pressure response to static handgrip exercise. ISH patients aged between 60 and 74 years were randomly divided into a control group (10 subjects, 4 of which were male) that breathed normally and a trained group (10 subjects, 4 of which were male) that trained daily for 8 weeks by slow breathing against an inspiratory resistance of 18 cmH2O. Before and immediately after training, subjects underwent a 2-min handgrip test (30% max) followed by 2 min of post-exercise circulatory occlusion (PECO) to assess metaboreflex activity. Training reduced sBP by 10.6 mm Hg (95% confidence interval (CI), -16 to -5 mm Hg, P=0.004), but changes were not observed in the control group. The peak exercise sBP was reduced by 23 mm Hg (95% CI, -16 to -31 mm Hg, P<0.001), while the increase in the sBP above resting was reduced by 12.6 mm Hg (95% CI, -6.9 to -18.2 mm Hg, P=0.002). The sBP during PECO was reduced by 8.9 mm Hg (95% CI, -4 to -14 mm Hg, P=0.008), which is indicative of reduced metaboreflex activity; no such change was observed in the control group. The results demonstrate that conventional treatment of older patients with ISH may be improved in two ways by slow breathing training: resting sBP may be reduced by 10 mm Hg, more than can be achieved by conventional pharmacological therapies, while the response to static exercise may be reduced by approximately twice this value.