Background: Platelet-to-lymphocyte ratio (PLR) is an inflammation index suggested to have the prognostic capability in heart failure (HF). We sought to investigate the association of PLR with cardiovascular disease (CVD) mortality and creatinine (Cr) rise among Iranian individuals suffering from acute decompensated HF (ADHF).Methods: This retrospective cohort study was in the context of the Persian Registry Of cardioVascular diseasE/Heart Failure (PROVE/HF) study. 405 individuals with ADHF admitted to the emergency department were recruited from April 2019 to March 2020. PLR was calculated by division of platelet to absolute lymphocyte counts and categorized based on quartiles. We utilized the Kaplan–Meier curve to show the difference in mortality based on PLR quartiles. Cr rise was defined as the increment of at least 0.3 mg/dl from baseline. Cox proportional hazard ratio (HR) was used to investigate the association of PLR with CVDs mortality.Results: Mean age of participants was 65.9 ± 13.49 years (males: 67.7%). The mean follow-up duration was 4.26 ± 2.2 months. CVDs mortality or re-hospitalization was not significantly associated with PLR status. Multivariate analysis of PLR quartiles showed a minimally reduced likelihood of CVDs death in 2nd quartile versus the first one (HR 0.40, 95% confidence interval (CI) 0.16–1.01, P = 0.054). Cr rise had no remarkable relation with PLR status in neither model.Conclusion: PLR could not be used as an independent prognostic factor among ADHF patients. Several studies are required clarifying the exact utility of this index.