In the recent Italian Network on Heart Failure (IN-HF) Outcome registry, including 1,855 patients with acute heart failure (AHF), we reviewed the use of inotropes and their prognostic implication on in-hospital and 12-month mortality. IN-HF Outcome is a prospective, multicenter, observational, study involving 61 Italian cardiology centers. AHF patients have been enrolled over a 2-year period and followed-up for 1 year. Inotropes were used in 360 patients (19.4%). Patients who received inotropes had a more severe clinical and hemodynamic profile than those who did not and exhibited a significantly higher rate of in-hospital (21.4% vs 2.7%, p < 0.01) and 1-year (50.6% vs 17.7%, p < 0.01) mortality. At entry, systolic blood pressure (SBP) was ≤ 110 mm Hg in 58%, 111 to 130 mm Hg in 24.5%, and > 130 mm Hg in 17.5%. Multivariable analyses showed use of inotropes was the strongest predictor of all-cause death. These data were confirmed by propensity score analyses. According to SBP at entry, the 2 groups with SBP > 110 mm Hg who took inotropes, despite a more favorable clinical profile, exhibited a similar worse prognosis, particularly at 1 year: 56.3% (≤ 110 mm Hg), 43.7% (111-130 mm Hg), and 40.3% (>130 mm Hg) vs 17.7%. Inotropes were used in nearly 20% of the patient admitted for AHF, and this treatment was associated with a short-term to medium-term poor prognosis. An inappropriate use of inotropes in patients with normal to high SBP, and presumably preserved cardiac output, may have significantly contributed to affect the all-group outcome.