Objectives: We investigated the comparative accuracy of renal translesional pressure gradients (TPG), intravascular ultrasound (IVUS), and angiographic parameters in predicting hypertension improvement after stenting of renal artery stenosis (RAS). Background: The degree of RAS that justifies stenting is unknown. Methods: In 62 patients with RAS, TPG (resting and hyperemic systolic gradient [HSG], fractional flow reserve, and mean gradient) were measured by a pressure guidewire; IVUS and angiographic parameters (minimum lumen area and diameter, area stenosis, and diameter stenosis) were measured by quantitative analyses. Results: The HSG had a larger area under the curve than most other parameters and an HSG ≥21 mm Hg had the highest sensitivity, specificity, and accuracy (82%, 84%, and 84%, respectively) in predicting hypertension improvement after stenting of RAS. The average IVUS area stenosis was markedly greater in RAS with an HSG ≥21 mm Hg versus <21 mm Hg (78% vs. 38%, respectively; p < 0.001). After stenting, hypertension improved in 84% of patients with an HSG ≥21 mm Hg (n = 36) versus 36% of patients with an HSG <21 mm Hg (n = 26) at 12 months, p < 0.01; the number of antihypertensive medications was significantly lower in patients with an HSG ≥21 mm Hg versus <21 mm Hg (2.30 ± 0.90 vs. 3.40 ± 0.50, respectively; p < 0.01). By multivariable analysis, HSG was the only independent predictor of hypertension improvement (odds ratio: 1.39; 95% confidence interval: 1.05 to 1.65; p = 0.013). Conclusions: An HSG ≥21 mm Hg provided the highest accuracy in predicting hypertension improvement after stenting of RAS, suggesting that an HSG ≥21 mm Hg is indicative of significant RAS. © 2009 American College of Cardiology Foundation.