OBJECTIVES: to compare the total treatment duration cost per patient between the two most used low-molecular-weight heparins (LMWHs) in Spain for the prophylaxis of the venous thromboembolism disease (VTE) and the treatment of deep vein thrombosis (DVT) with and without pulmonary embolism (EP), during the acute phase and at long term.  METHODS: patients in prophylaxis were classified as moderate or high according to the risk of the surgery. Patients with high risk were further classified by surgery type: 1) orthopedic or oncologic surgery, 2) other surgeries, and 3) medical patients (surgery is not performed by a surgical speciality but other specialists). Patients with DVT were divided into 10 kilogramme weight ranges as well as considering the distribution of the Spanish population in each range taken from the RIETE registry. Treatment duration was obtained from clinical guidelines. Treatment duration and patient profile defined the strength and package size used to estimate the cost per patient in prophylaxis. Concerning DVT, only the most appropriate strengths for each weight range were considered. Costs are expressed in € of 2015 and calculated based on the retail price plus the value-added tax of each LMWH discounting the corresponding deduction according to Royal Decrees.  RESULTS: administering enoxaparine instead of bemiparine represents a saving of 6€ (5%), 7€ (16%) and 7€ (16%) per patient per total treatment duration with high risk undergoing surgery type 1, 2 and 3, respectively, and 4€ (16%) per patient per total treatment duration with moderate risk. Average savings per patient per total treatment duration with DVT came to 61€ (56%) and 354€ (46%) in the acute phase and at long term, respectively.  CONCLUSIONS: the cost of treating VTE or DVT is lower when administering enoxaparine instead of bemiparine. Therefore, the use of enoxaparine represents an economic benefit for the Spanish health system.