Background: Traditional procurement and price negotiation methods in public hospitals in Thailand involve group purchasing agreements and bulk orders, posing challenges to improving inventory management efficiency. The vendor-managed inventory (VMI) model is a promising alternative for enhancing hospital performance, especially during crises. This study aimed to assess the potential cost savings in implementing VMI in a large general hospital in Thailand. Methods: A simulation modeling approach was used to compare the current inventory system with three VMI models: VMI1, focused on improving inventory turnover rate (ITR); VMI2, emphasized frequent replenishment with a 1-month supply; and VMI3, eliminated safety stock. Results: The results demonstrated significant cost savings, with potential reductions in total inventory management expenses. Specifically, VMI1 improved ITR from 6.31 to 7.76, reducing average inventory by 36% and cutting management costs by 40%. VMI2, with an ITR of 12.80, reduced inventory by 44% and saved 47% in management costs, while VMI3 achieved a 70% reduction in inventory and a 69% saving in management costs. Conclusions: This study highlights the VMI’s transformative potential in hospital inventory management, demonstrating significant cost savings. However, in the public sector, the feasibility of procurement regulations requires further exploration.