Isolated systolic hypertension is common in the elderly, but decreasing systolic blood pressure (SBP) without lowering diastolic blood pressure (DBP) remains a therapeutic challenge. Although stress management training, in particular eliciting the relaxation response, reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated. We conducted a double-blind, randomized trial comparing 8 weeks of stress management, specifically relaxation response training (61 patients), versus lifestyle modification (control, 61 patients). Inclusion criteria were >or=55 years, SBP 140-159 mm Hg, DBP <90 mm Hg, and at least two antihypertensive medications. The primary outcome measure was change in SBP after 8 weeks. Patients who achieved SBP <140 mm Hg and >or=5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination. SBP decreased 9.4 (standard deviation [SD] 11.4) and 8.8 (SD 13.0) mm Hg in relaxation response and control groups, respectively (both ps <0.0001) without group difference (p=0.75). DBP decreased 1.5 (SD 6.2) and 2.4 (SD 6.9) mm Hg (p=0.05 and 0.01, respectively) without group difference (p=0.48). Forty-four (44) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination. After controlling for differences in characteristics at the start of medication elimination, patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication (odds ratio 4.3, 95% confidence interval 1.2-15.9, p=0.03). Although both groups had similar reductions in SBP, significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control.