Introduction: Loop diuretic resistance (LDR) is a risk factor for poor prognosis in patients with acute heart failure (AHF). Acidic urine (pH <6) might be associated with diminished effect of diuretics and worse in-hospital course in this patient population. Objectives: The aim of the study was to assess the influence of acidic urine on in-hospital prognosis and diuretic efficacy in patients with AHF. Patients and methods: This was a retrospective analysis of hospitalizations due to AHF in patients with ejection fraction of 50% or less. Analyzed end points were: in-hospital death and composite end point (death, myocardial infarction, stroke, unplanned revascularization, or catecholamine infusion). Diuretic efficacy was assessed as diuresis per intravenous furosemide dose equivalent. Receiver operating characteristic curve analysis for in-hospital death was used to set a cutoff value for diuretic resistance. Logistic regression analysis was used to select independent risk factors for the occurrence of in-hospital death, composite end point, and LDR. Results: A total of 373 hospitalizations (300 patients) were analyzed. Urine pH of less than 6 on admission was present in 158 cases (42.1%). In-hospital mortality was 7.5% in cases with nonacidic urine as compared with 15% of those with acidic urine (P = 0.03). Composite end point occurred in 10% of patients with nonacidic urine as compared with 31% of those with acidic urine (P <0.001). Acidic urine was found to be an independent risk factor for the composite end point. The threshold for LDR was set at 691.45 ml of diuresis/40 mg of intravenous furosemide. Low urine pH was found to be an independent risk factor for LDR. Conclusions: Low urine pH might be a useful marker identifying patients at high risk for LDR and adverse in-hospital outcome.