Current guidelines recommend that inotropes should not be used in patients with normal systolic blood pressure (SBP). However, this is not supported with concrete evidence. We aimed to evaluate the effect of inotropes in acute heart failure (HF) patients from a nationwide HF registry. A total of 5625 patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. The primary outcomes were in-hospital adverse events and 1-month mortality. Among the total population, 1703 (31.1%) received inotropes during admission. Inotrope users had a higher event rate than non-users (in-hospital adverse events: 13.3% vs. 1.4%, p < 0.001; 1-month mortality: 5.5% vs. 2.5%, p < 0.001), while inotrope use was an independent predictor for clinical outcomes (in-hospital adverse events: OR_adjusted 5.459, 95% CI 3.622⁻8.227, p < 0.001; 1-month mortality: HR_adjusted 1.839, 95% CI 1.227⁻2.757, p = 0.003). Subgroup analysis showed that inotrope use was an independent predictor for detrimental outcomes only in patients with normal initial SBP (≥90 mmHg) (in-hospital adverse events: OR_adjusted 5.931, 95% CI 3.864⁻9.104, p < 0.001; 1-month mortality: HR_adjusted 3.584, 95% CI 1.280⁻10.037, p = 0.015), and a propensity score-matched population showed consistent results. Clinicians should be cautious with the usage of inotropes in acute heart failure patients, especially in those with a normal SBP.