Background Hyponatremia has been known as an important predictor of clinical outcomes in patients with heart failure (HF). While information on hyponatremia in patients with HF has been available abundantly, information on factors associated with increased risk of developing hospital-acquired hyponatremia (HAH) is still limited. Objective To identify patients and medication-related factors associated with HAH in patients hospitalized from HF. Setting Fatmawati Hospital in Jakarta, Indonesia. Methods This is a nested case-control study with patients developing HAH served as case group and each patient in case group was matched by age and gender to three patients in control group. Patients included in this study are patients hospitalized from HF, and coded with I.50 according to ICD-10, during 2011-2013 at Fatmawati Hospital in Jakarta, Indonesia. Information retrieved from patients' medical records included demographic profiles, vital signs and symptoms at admission, past medical history, medication during hospitalization and clinical chemistry laboratory records. Multivariable logistic regression analysis was performed to find out patient and treatment-related factors associated with the development of HAH. Main outcome measures Patients and medication related factors having significant association with HAH. Results Four hundreds sixty-four patients were included in this study and 45 of them (9.7 %) met criteria of developing HAH so then, accordingly, 135 patients were selected as controls. 36 patient- and 22 treatment-related factors were analyzed in univariate logistic regression resulted in 20 factors having p value <0.2 and were included in multivariable logistic regression analysis. Final factors showing significant association with HAH are presence of ascites at admission (odds ratio = 4.7; 95 % confidence interval 1.9-11.5) and administration of amiodarone (3.2; 1.3-7.4) and heparin (3.1; 1.2-7.3) during hospital stay. Conclusion Presence of ascites at admission was found as patient-related factors associated with HAH in this study. In addition, administration of amiodarone and heparin during hospital stay were found as medication-related factors associated with HAH in patients hospitalized from HF.