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Background: Kidney dysfunction (KD) is a main limiting factor of applying guideline‐directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). Hypothesis: We aimed to assess the success of optimization, long‐term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + βB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. Methods: The data of 247 real‐world, consecutive patients were analyzed who were hospitalized in 2019−2021 for HFrEF and then were followed‐up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60−89, 45−59, 30−44, <30 mL/min/1.73 m2). Moreover, 1‐year all‐cause mortality and rehospitalization rates in KD subgroups were investigated. Results: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p <.05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p <.05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One‐year all‐cause mortality (14%, 15%, 16%, 33%, 48%, p <.001), the ratio of all‐cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p =.028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p =.001) were significantly higher in more severe KD categories. Conclusions: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up‐titration of GDMT. [ABSTRACT FROM AUTHOR]