Heart failure (HF) is a major contributor of cardiovascular morbidity and mortality globally. Despite its adverse impact on health outcomes in low- and middle-income countries such as Kenya, data on the direct medical cost of HF hospitalization is limited. This was a prospective study conducted at Moi Teaching and Referral Hospital. Patients with HF were identified by sequential medical chart abstraction. Primary causes were extracted from echocardiogram reports and adjudicated by a cardiologist. Direct medical cost of hospitalization was derived using activity-based costing, micro-costing method, and payers’ system perspective. Drivers of overall cost were explored using linear regression models. 142 participants were consecutively recruited from September to November 2022. 51.4% were females, and the overall mean age was 54 (SD 20). The leading primary cause was cor pulmonale (CP), 28.9%; then dilated cardiomyopathy (DCM), 26.1%; rheumatic heart disease (RHD), 19.7%; hypertensive heart disease (HHD), 16.9%; ischaemic heart disease (IHD), 6.3%; and pericardial disease (PD), 2.1%. Overall direct cost of HF hospitalization was Kshs. 11,470.94 (SD 8,289.57) per patient per day, with the mean length of hospital stay of 10.1 (SD 7.1). RHD incurred the highest costs, Kshs. 15,299.08 (SD 13,196.89) per patient per day, then IHD, Kshs. 12,966.47 (SD 6656.49), and DCM, Kshs.12,268.08 (SD 7,816.12). Cost of medications was the leading driver, β = 0.56 (0.55 – 0.56), followed by inpatient fees, β = 0.27 (0.27 – 0.28) and laboratory investigations, β = 0.19 (0.18 – 0.19). Cor pulmonale, CM, RHD and HHD were the major causes of HF. The overall direct medical cost of hospitalization was extremely expensive compared with the average monthly household income per capita in Kenya. Widespread insurance cover is therefore recommended to cushion families against such catastrophic health expenditures beside public health measures aimed at addressing primary causes of HF.