OBJECTIVE: To generate estimates of the cost-effectiveness of thromboprophylaxis with enoxaparin versus no thromboprophylaxis (usual care) in patients with acute medical illness in the health care setting of Brazil from the perspective of the public Brazilian health care system. METHODS: Markov process analysis techniques were used to model the health economic outcomes. Data on probabilities of clinical events were derived from clinical trial data from the MEDENOX trial, other published literature and OECD (Organisation for Economic Co-Operation and Development) country-specific population mortality data; units of health care utilization were derived from the Delphi panels; prices and tariffs were derived from official lists. RESULTS: Analysis over a 1-year period showed that the cost per VTE event avoided was REAL 2,349 (US$870; €906) and the cost per life saved was REAL 8,296 (US$3,073; €3,201), when assuming no higher risk for morbidity and mortality for asymptomatic patients. The lifetime model (again, assuming no higher risk for recurrence of VTE for asymptomatic patients), showed that the use of enoxaparin leads to a cost per VTE event avoided of REAL 2,194 (US$813; €846) and cost per life year gained of REAL 574 (US$213; €221). The lifetime model, which assumes a higher risk of VTE recurrence in asymptomatic patients, leads to a cost of REAL 317 (US$117; €122) per VTE event avoided and REAL 90 (US$33; €35) per life year gained. CONCLUSION: The results showed that the favourable clinical benefit of enoxaparin results in positive short and long-term health economic benefits.