Background Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. Study Design Single-center prospective cohort study; retrospectively analyzed. Setting & Participants 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. Predictors Presentation with flash pulmonary edema (n = 37 7.8%), refractory hypertension (n = 116 24.3%), or rapidly declining kidney function (n = 46 9.7%) compared to low-risk presentation with none of these phenotypes (n = 230 49%). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. Outcomes Death, cardiovascular (CV) event, end-stage kidney disease. Results During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P  < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P  < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P  = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P  = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P  = 0.02). Limitations Observational study; retrospective analysis; potential treatment bias. Conclusions This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.