Purpose Platelet transfusions (PT) are commonly used as prophylaxis in patients with chronic liver disease (CLD) and severe thrombocytopenia (TCP) before invasive procedures, in order to reduce risk of bleeding. The aim of this cost analysis was to generate a comprehensive estimate of costs of platelet transfusions in Italy, focusing on patients with severe TCP due to CLD undergoing an elective procedure. Methods The research was conducted in different phases: 1) assessment of a pre-specified framework for the identification of processes related to PT; 2) estimation of resource consumption through Delphi technique and collection of unit costs through literature; 3) development of a cost analysis to estimate the overall average costs per PT, focusing on a representative patient with CLD and severe TCP. Robustness of results was tested in a sensitivity analysis. Results Despite the lack of some cost components estimation and uncertainty related to event probability, the analysis showed a total cost of 5297 € for each PT in patients with CLD and severe TCP. The total cost was largely driven by direct costs (4863 €) associated with platelet collection, transfusion, and management of refractoriness, which accounted for 92% of total. Conclusion In an environment of limited resources, it is crucial for the healthcare service to have accurate and inclusive information on transfusion costs, incorporating not only the cost of blood products but also those related to collection and management. The analysis showed that platelet collection and administration costs add substantially to the cost of platelet products themselves. As expected, the highest cost was the transfusion process itself (44% of total), followed by refractoriness (43% of total). Since limited literature exists concerning these cost estimates, this analysis represents a step forward in understanding the economic burden of patients with CLD and severe TCP scheduled to undergo an invasive procedure.