Background: Several medications may worsen heart failure (HF), and they are considered as potentially inappropriate medications for patients with heart failure (PIMHF). No studies have reported the prevalence of PIMHF use and its associated factors in Thai HF patients. Objective: To determine the prevalence of PIMHF use and identify the factors associated with PIMHF use. Materials and Methods: A cross-sectional analytical study was conducted using data on HF patients obtained from the electronic medical databases (EMD) of two hospitals, including a secondary- and a tertiary-care hospital. Data collected included demographics, diagnoses, and medication items prescribed during 2016–2019. The prevalence of PIMHF use identified by the Thailand list of PIMHF was determined. Patient and clinical factors were examined for association with PIMHF use by calculating the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) using a binary logistic regression analysis. Results: From the EMD, 972 and 2,888 eligible HF patients from a secondary- and a tertiary-care hospital, respectively, were included in this study. The prevalence of PIMHF use was 45.16% and 33.07% at a secondary- and a tertiary-care hospital, respectively. The PIMHF distribution appeared similar between the two study hospitals, with oral corticosteroids being the most frequently prescribed, followed by NSAIDs, COX-2 inhibitors, and thiazolidinediones. The factors associated with PIMHF use were non-cardiovascular (non-CVD) co-morbidities, including diabetes mellitus (aOR = 1.68, 95%CI = 1.42–1.99), chronic pulmonary diseases (aOR = 2.69, 95%CI = 2.07–3.48), connective tissue diseases (aOR = 7.16, 95%CI = 3.09–16.57), and cancer (aOR = 1.97, 95%CI = 1.20–3.22). Conclusion: PIMHF use was prevalent in Thai HF patients and associated with certain non-CVD co-morbidities. A careful prescription and a review of medication use should focus on HF patients with specific non-CVD co-morbidities. Keywords: Heart failure; Potentially inappropriate medications; Thailand criteria; Prevalence; Factors associated