We aimed to investigate the association between the pan-immune-inflammation value (PIV) and mortality in patients with heart failure with a reduced ejection fraction (HFrEF), along with clinical and biochemical parameters. : In this retrospective cohort study, 419 patients diagnosed with HFrEF between January 2014 and December 2023 were analyzed. Data on demographic features, comorbidities, cardiac parameters [New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), ventricular dimensions], medication use, and laboratory findings (PIV, N-terminal pro-B-type natriuretic peptide [NT-proBNP], electrolytes, and complete blood count) were collected from institutional and national records. : Mortality occurred in 22.91% of patients. PIV > 696 was significantly associated with mortality (sensitivity: 37.5%, specificity: 78.64%, = 0.006), but it was not an independent predictor in multivariate analysis. Instead, low body mass index (BMI), increased end-systolic diameter, reduced LVEF, advanced NYHA class (III/IV), elevated NT-proBNP, hyponatremia, and lymphopenia were identified as independent predictors (all < 0.001). : Although PIV was associated with mortality in patients with HFrEF, it did not independently predict outcomes beyond established risk factors. These results suggest that while inflammation may contribute to HFrEF pathophysiology, traditional clinical and biochemical markers remain more reliable for prognostication.