The objective of this prespecified TRINITY study subgroup analysis was to assess the efficacy and safety of triple-combination treatment with olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg vs the component dual-combination treatments in obese (body mass index [BMI] ≥30 kg/m2) and nonobese (BMI <30 kg/m2) hypertensive participants. The double-blind treatment period primary end point was the least-squares (LS) mean reduction in seated diastolic BP (SeDBP) at week 12 (end of the double-blind period). Of the 2492 randomized participants, 1555 (62.4%) had BMI ≥30 kg/m2. Irrespective of BMI, triple-combination treatment resulted in greater LS mean reductions in seated BP (SeBP) (≥30 kg/m2, 6.7–10.5/4.5–7.3 mm Hg; <30 kg/m2, 5.1–8.6/2.5–6.0 mm Hg [P<.005] vs dual-combination treatments for both subgroups) at week 12. Furthermore, triple-combination treatment enabled a greater proportion of participants to reach BP goal vs the dual-combination treatments (≥30 kg/m2, 62% vs 31%–46% [P<.0001]; <30 kg/m2, 69% vs 41%–55% [P<.005]) at week 12. SeBP reduction and goal attainment (≥30 kg/m2, 63%; <30 kg/m2, 67%) was maintained through week 52/early termination. Triple-combination treatment was well tolerated in both BMI subgroups.