Treatment of heart failure (HF) in the elderly face many difficulties due to lack of robust evidence. We analyzed the outcome of HF in octogenarians using a nationwide HF registry. Among 5625 patients from the Korean Acute Heart Failure (KorAHF) registry, prognosis of octogenarian HF and the association of guideline-directed medical therapy (GDMT) with mortality and readmissions were analyzed. Octogenarian patients (1185, 22.4%) showed a higher mortality, and males were especially at increased risk (HR (hazard ratio) 1.19, 95% CI 1.01–1.40). A J-curve association between blood pressure (BP) and mortality was observed regardless of age, but the nadir value was lower in octogenarians (123.8 vs. 127.9 mmHg for systolic blood pressure (SBP); 67.1 vs. 73.9 mmHg for diastolic blood pressure (DBP), p < 0.001). Use of GDMT in octogenarian patients with HF and reduced ejection fraction (EF) were inadequate (74.3%, 47.1%, and 46.1% in octogenarians vs. 78.4%, 59.8%, and 55.2% in non-elderly for renin-angiotensin system inhibitors, beta-blockers, and aldosterone antagonists, respectively; all p < 0.05). However, those on medications had a significant reduction in 6 month mortality. For octogenarians with HF and preserved EF, angiotensin receptor blocker use reduced hospitalizations for HF in men (HR 0.19, 95% CI 0.04–0.87), but not in women (p-interaction = 0.037). HF in octogenarians were found to have different characteristics compared with the non-elderly. However, adequate use of GDMT was still associated with improved survival, and more attention should be given to prescribing medications with clinical benefits.