OBJECTIVES: A decision-analytic model using cost data and clinical information from the PREVAIL study showed that enoxaparin was cost-saving from the payer perspective compared with unfractionated heparin (UFH) for the prevention of venous thromboembolism (VTE) in patients with acute ischemic stroke (overall costs of clinical events plus drug costs: $2018 vs. $2913, respectively; difference $895 per patient). To test the robustness of the cost difference of enoxaparin versus UFH for VTE prevention after an acute ischemic stroke, univariate and multivariate sensitivity analyses were performed.  METHODS: In the univariate analysis, the payer cost (2007$) for each clinical event (deep-vein thrombosis [DVT], pulmonary embolism [PE]; intracranial hemorrhage [ICH], major extracranial hemorrhage [MjEH] and minor extracranial hemorrhage [MnEH]) was adjusted individually, increasing or decreasing by 20%, while other parameters (drug costs, event rates) remained unchanged. The multivariate analysis was a Monte Carlo simulation (Crystal Ball software), where all the parameters were simultaneously varied in a random fashion within a range of ±20% over 10,000 trials. RESULTS: The cost of DVT was $13,499. When increased by 20% to $16,199, the difference between UFH and enoxaparin groups was $1,104; when decreased by 20% to $10,799, the difference was $686. The baseline costs were $20,635 for PE, $26,037 for ICH, $22,765 for MjEH and $815 for MnEH. When these were increased by 20%, the difference between enoxaparin and UFH groups was $928, $907, $859 and $896, respectively. When decreased by 20%, the difference was $862, $883, $932 and $894. Using the Monte Carlo simulation multivariate analysis, the difference varied between $615 and $1,177, with mean (SD) $896 ($91) and median of $897. Enoxaparin was less costly than UFH across all analyses, with DVT being the main cost driver. CONCLUSIONS: Univariate and multivariate sensitivity analysis confirmed that enoxaparin is more cost-saving than UFH for VTE prevention after an acute ischemic stroke.