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SUMMARY Objectives: To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. Background: Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end‐organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. Methods: We describe the bottom‐up, time‐driven, activity‐based costing methodology used to develop process maps to provide a step‐by‐step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. Results: Thirty‐one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. Conclusions: Detailed process maps using bottom‐up, time‐driven, activity‐based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings. [ABSTRACT FROM AUTHOR]