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Meta-analyses have shown that supervised isometric handgrip training reduces blood pressure in hypertensives. However, the mechanism(s) underlying these effects in medicated hypertensive patients, as well as the effects from home-based exercise training, is uncertain. The purpose of this study was to compare the effects of supervised and home-based isometric handgrip training on cardiovascular parameters in medicated hypertensives. In this randomized controlled trial, 72 hypertensive individuals (38–79 years old, 70% female) were randomly assigned to three groups: home-based, supervised isometric handgrip training or control groups. Home-based and supervised isometric handgrip training was completed thrice weekly (4 × 2 min at 30% of maximal voluntary contraction, with 1-min rest between bouts, alternating the hands). Before and after 12 weeks brachial, central and ambulatory blood pressures (BP), arterial stiffness, heart rate variability, vascular function, oxidative stress and inflammation markers were obtained. No significant (p > 0.05) effect was observed for ambulatory BP, arterial stiffness, heart rate variability, vascular function and oxidative stress and inflammatory markers in all three groups. Brachial BP decreased in the supervised group (Systolic: 132 ± 4 vs. 120 ± 3 mmHg; Diastolic: 71 ± 2 vs. 66 ± 2 mmHg, p < 0.05), whereas no significant differences were observed in the home-based (Systolic: 130 ± 4 vs. 126 ± 3 mmHg; diastolic: 73 ± 3 vs. 71 ± 3 mmHg) and control groups (p > 0.05). Supervised handgrip exercise also reduced central BP systolic (120 ± 5 vs. 109 ± 5 mmHg), diastolic (73 ± 2 vs. 67 ± 2 mmHg); and mean BP (93 ± 3 vs. 84 ± 3 mmHg), whereas no significant effects were found in the home-based (Systolic: 119 ± 4 vs. 115 ± 3 mmHg; Diastolic: 74 ± 3 vs. 71 ± 3 mmHg) and control groups (p > 0.05). In conclusion, supervised, but not home-based, isometric training lowered brachial and central BP in hypertensives.