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Introduction Serum chloride has been recently recognised as a predictor of short-term mortality in patients hospitalised with acute heart failure (AHF). However, data from developing nations such as Vietnam remain limited.Methods We conducted a cross-sectional study at Can Tho Central General Hospital, Vietnam, from May to December 2024. Adult patients aged ≥18 years, hospitalised with AHF and NT-proBNP levels ≥300 pg/mL, were included after providing informed consent. Exclusions were made for patients lacking 24-hour electrolyte panels, those transferred or deceased before blood collection and individuals with end-stage renal disease, on renal replacement therapy or with active malignancies. Postdischarge survivors were followed up via phone interviews for 30 days. The primary endpoint was all-cause mortality. Given the low in-hospital event rate (5%), logistic regression was used to estimate ORs, while modified Poisson regression with robust variance estimation was applied for 30-day mortality, where the event rate exceeded 10% and OR would overestimate true risk.Results The final cohort included 423 patients (mean age 69.7±12.7 years; 48% male). During hospitalisation, 21 (5.0%) patients died and 402 were discharged alive. Of the discharged patients, 252 (62.7%) completed a 30-days follow-up, with 43 deaths (17.1% mortality rate). After adjusting for age, sex, coronary artery disease, chronic heart failure, left ventricular ejection fraction and serum sodium, hypochloraemia was an independent predictor of in-hospital mortality (adjusted OR 4.9; 95% CI 1.3 to 18.5) and 30-days mortality (adjusted RR 1.9; 95% CI 1.1 to 3.6). Additionally, each 1 mmol/L increase of chloride was associated with a 5% lower risk of 30-day death (RR per unit change 0.95; 95% CI 0.91 to 0.99; p=0.007).Conclusion Admission serum chloride levels independently predicted both in-hospital and 30-days all-cause mortality in Vietnamese patients with AHF. Including this biomarker in risk-stratification tools could enhance short-term prognostication, while its longer-term predictive value warrants further investigation.