Background: Serum natriuretic peptide (NT-proBNP) is a critical biomarker for diagnosing left ventricular dysfunction. Heart failure is the leading cause of mortality in chronic kidney disease (CKD), emphasizing the need for its early detection and prognosis. Objective: This study aimed to determine the serum NT-proBNP levels in participants with CKD and establish a cut-off value for predicting heart failure. Methods: A descriptive cross-sectional study was conducted from April 1 to July 1,2024. This study received approval from the Ethics Committee of the Institute of Medical Sciences (Approval No.24/01). A total of 117 CKD patients hospitalized in the Nephrology and Endocrinology Department of the third state hospital were enrolled based on predefined inclusion and exclusion criteria. Data were collected using questionnaires, laboratory and heart ultrasound test results. Serum NT-proBNP levels were measured using a rapid immunofluorescence quantitative analyzer. Data were analyzed with SPSS 26.0. Results: The mean age of the 117 participants was 57.9 ± 14.7 years, with 51.3% being male. The mean serum NT-proBNP level was 7686 ± 12149 pg/mL. Statistically significant differences were observed in serum creatinine, sodium, calcium, CKD stage, and arterial hypertension between genders (p<0.05). NT-proBNP levels in hemodialysis patients differed significantly between heart failure and non-heart failure groups (p<0.05). Significant differences were also found in hemoglobin, serum albumin, NT-proBNP levels, and CKD stages (p<0.05). NT-proBNP correlated significantly with risk factors such as hemodialysis, diabetes, and decreased systolic blood pressure (p<0.0001). A weak inverse relationship was noted between systolic blood pressure and NT-proBNP (R² = 0.16). The NT-proBNP cut-off value for predicting heart failure was 3027 pg/mL, with an AUC of 61.7% (sensitivity: 74.5%, specificity: 55%). Conclusion Serum NT-proBNP levels are elevated in CKD patients regardless of heart failure. The established cut-off value for NT-proBNP in CKD patients to detect heart failure was 3027 pg/mL, with moderate diagnostic utility (AUC = 61.7%).