Background To estimate the cost-effectiveness of sterile cold spray for improving 12-month repeat donation among first-time whole blood donors aged 18–25 years in mainland China from a blood-centre perspective.Methods We developed a 12-month Markov model from a blood-centre perspective comparing a sterile vapocoolant spray (cold spray) with standard care in first-time whole-blood donors aged 18–25 years in mainland China. Trial-based short-term changes in pain (VAS) and anxiety (BDAS) were translated to 12-month repeat donation using a Theory of Planned Behaviour pathway with a calibration parameter informed by domestic retention data. Incremental costs (consumables, staff time, and training) were estimated using time-driven activity-based costing from three blood centres (2023–2024). Uncertainty was assessed using one-way sensitivity analysis and probabilistic sensitivity analysis (5,000 simulations). No patients or members of the public, including blood donors, were involved in the design, conduct, or reporting of this model-based cost-effectiveness analysis.Conclusion Cold spray is estimated to improve first-time donor experience and is likely to be cost-effective for improving 12-month donor retention under commonly used blood-centre willingness-to-pay thresholds in China.