The superior diastolic blood pressure reduction (BP) of high-dose combination therapy with trandolapril (Tr) and verapamil-SR (Ve) compared with monotherapy has previously been reported. Guideline changes, placing greater emphasis on systolic BP, prompted a re-evaluation of TV-51 and an assessment of a subset of patients from the INternational VErapamil-SR Trandolapril STudy (INVEST). The objective of this analysis was to determine if the short-term antihypertensive effects of high-dose Tr+Ve (Tr/Ve study) could be confirmed in a sample of higher-risk INVEST patients with longer follow-up. The Tr/Ve study was a double-blind, randomized, parallel-group, placebo-controlled trial to evaluate the antihypertensive effects of trandolapril and verapamil-SR alone or in combination in 631 patients randomized to placebo, 4 mg trandolapril, 240 mg verapamil-SR or 4 mg/240 mg Tr+Ve combination for 6 weeks; 581 INVEST patients were selected for comparison with 24-month BP data, 90% use of trandolapril and verapamil-SR combination therapy and no triple therapy. Tr+Ve combination treatment achieved significantly greater systolic and diastolic BP reduction versus monotherapy. The BP-lowering effects of high-dose Tr+Ve achieved during short-term treatment were confirmed in INVEST during longer follow-up. Despite differences in the risk profiles of previously studied patients and INVEST patients, the antihypertensive effects of Ve+Tr were similar.