This study evaluated the cost-effectiveness of platelet-rich plasma (PRP) added to usual care versus usual care alone in elderly patients with chronic diabetic foot ulcer (DFU) from the Spanish health care system perpective. A 6-state Markov model with 3-month cycles was used to estimate costs and outcomes of wound healing and risk of recurrences, infections, and amputations over 5 years. Three treatment strategies were compared: ( a) usual care plus PRP obtained with a commercial kit, ( b) usual care plus PRP obtained manually, and ( c) usual care. Data on effectiveness were taken from a recent meta-analysis. Outcomes and costs were discounted at 3% and resources were valued in 2018 euro. Compared with usual care, the PRP treatment with the manual method was more effective and less costly (dominant option), whereas the PRP treatment with the commercial kit was more effective but also more costly, with the incremental ratio being above the cost-effectiveness threshold (€57 916 per quality-adjusted life year). These results are sensitive to the price of PRP kits (a 20% discount would make the PRP treatment a cost-effective option) and effectiveness data, due to the heterogeneity of primary studies. In conclusion, PRP treatment for DFUs could be considered a cost-effective or even cost-saving alternative in Spain, depending on the method of obtaining the PRP. Despite the dominance of the manual method, its general use is limited to hospitals and specialized centers, whereas PRP kits could be used in primary care settings, but their prices should be negotiated by health authorities.