In many patients, the treatment of heart failure (HF) cannot be optimized because of pre‐existing or treatment‐induced hypotension. Midodrine, a peripheral α1‐adrenergic agonist may allow for up‐titration of neurohormonal antagonist therapy leading to improved outcomes. Ten consecutive patients with HF due to systolic dysfunction and symptomatic hypotension interfering with optimal medical therapy were started on midodrine. After a 6‐month follow‐up, a higher percentage of patients were on optimal HF therapy (angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker mg % of optimal dose 20% vs 57.5%; P<.001) (β‐blockers mg % optimal dose 37.5% vs 75%; P<.001) (spironolactone/eplerenone mg % 43.7% vs 95%; P<.001). This led to an improvement in left ventricular ejection fraction (baseline 24±9.4 vs 32.2±9.9; P<.001) and clinical outcomes, with a significant reduction in total hospital admissions (32 vs 12; P=.02) and total hospital days (150 vs 58; P=.02).