OBJECTIVES Venous thromboembolism (VTE) is a frequent but preventable complication in hospitalized patients. The objective of this population-based simulation was to estimate, for Saudi Arabia and using a British (NICE) model, the cost-efficiency of partial versus complete thromboprophylaxis of hospitalized adult patients at medium-to-very-high (M2VH)-VTE risk. METHODS Simulation including all 2012 Saudi adult medical (n=2,129,866) and surgical (n=964,033) hospital admissions, expressed in Saudi riyals (SAR), using three scenarios based on published real-world thromboprophylaxis studies: (1) international study and (2) Saudi subsample thereof (Cohen et al, Lancet 2008), and (3) Middle-Eastern study (Mokhtari et al, J Thromb Haemost 2011). Variables included rates for: high bleeding risk (mechanical versus pharmacoprophylaxis); major bleeding episode (MBE) secondary to pharmacoprophylaxis; deep vein thrombosis (DVT; pulmonary embolism (PE); and 12-month DVT/PE readmission following such discharge diagnosis. Costs considered were: thromboprophylaxis; management of MBE, DVT, PE; and 12-month DVT/PE readmission.  RESULTS Scenario (1): total costs for partial and complete prophylaxis were SAR631,462,830 and SAR508,957,517 for a complete-over-partial cost-avoidance by 24.1% of SAR122,505,313/year (SAR92.14 per patient and SAR167.83 per patient at VTE risk). Scenario (2): total costs for partial and complete prophylaxis were SAR712,441,824 and SAR600,483,584 for a complete-over-partial cost-avoidance by 18.6% of SAR111,958,239/year (SAR77.35 per patient and SAR127.58 per patient at VTE risk).  Scenario (3): total costs for partial and complete prophylaxis were SAR749,939,936 and SAR647,300,590 for a complete-over-partial cost-avoidance by 15.9% of SAR102,639,346/year (SAR62.77 per patient and SAR97.84 per patient at VTE risk).  CONCLUSIONS In this population-based cost-efficiency simulation for Saudi Arabia, thromboprophylaxis of all admitted M2VH-VTE risk versus partial methods is associated with significant cost savings per year.  Considering the associated reductions in DVT, PE, and readmissions, even under increased pharmacoprophylaxis-related MBE risk and costs, complete thromboprophylaxis of (M2VH)-VTE risk patients achieves the Institute for Healthcare Improvement Triple Aim of better care, better patient outcomes, and reduced costs.