OBJECTIVES: Evaluate adherence to the therapeutic prophylaxis protocol for venous thromboembolism (VTE) as well as the costs of this practice. METHODS: A descriptive and cross-sectional study was conducted at a State General Hospital in Brazil through reports of drug dispensions, prescriptions and risk stratification of patients. Adherence to the VTE prophylaxis protocol was monitored. The tests for VTE diagnosis measured the adherence to therapeutic prophylaxis treatment, and the purchase prices of the drugs went into the calculation of drug therapy costs. The level of adherence to prescriptions for VTE prophylaxis in the hospital was classified as “adherence”, “non-adherence” and “justified non-adherence” when compared with the protocol. RESULTS: Protocol adherence was observed for 50 (30.9%) patients, and non-adherence was observed for 63 (38.9%) patients, generating an additional cost of $180.40/month. Justified non-adherence in 49 (30.2%) patients generated $514.71/month in savings due to a reduction in the number of daily administrations of unfractionated heparin while still providing an effective method for preventing VTE. Twenty-six patients stratified as having medium to high risk of VTE who did not receive prophylaxis were identified, generating $154.41 in savings. However, these data should be evaluated with caution since the risks and outcomes associated with not preventing VTE outweigh the economy achieved from not prescribing a drug when a patient needs it. The only case of VTE identified during the study period was related to justified non-adherence to the protocol. CONCLUSION: The protocol is based on scientific evidence that describes an effective therapy to prevent VTE. However, the protocol should be updated because the justifications for non-adherence are based on scientific evidence, and this justified non-adherence generates savings and yields effective disease prevention.