<i>Objectives:</i> To evaluate physician-determined worsening heart failure (PD-WHF) in patients admitted with acute heart failure (AHF). <i>Methods:</i> The PROTECT pilot study evaluated rolofylline, an adenosine A₁ receptor antagonist, versus placebo in patients with AHF and renal impairment. Signs and symptoms of heart failure (HF) and diuretic administration were prospectively recorded daily for 7 days and patients were followed for 60 days. Patients were categorized into three groups: (A) PD-WHF, based on worsening symptoms and signs of HF and need for additional intravenous (IV) or mechanical therapy (n = 29); (B) increased IV diuretic therapy without PD-WHF (n = 61), and (C) neither PD-WHF nor increase in IV diuretic dose (n = 211). <i>Results:</i> Patients in group A had slower resolution of dyspnea, longer mean (±SD) length of hospitalization (13.8 ± 6.8 vs. 10.5 ± 8.5 and 9.3 ± 5.9 days in groups B and C, respectively; p < 0.05 for both), and higher 60-day death and cardiovascular or renal readmission rates [49.7 (95% confidence interval: 33.1–69.1) vs. 37.3 (26.4–50.9) vs. 19.5% (14.7–25.6) in groups B and C, respectively]. PD-WHF was a strong independent predictor of length of stay and 60-day death and cardiovascular or renal readmission. <i>Conclusions:</i> PD-WHF may be an indicator of short-term risk and treatment efficacy in AHF.