Introduction Total knee arthroplasties have the purpose to improve quality of life from joint-related pain. On the other hand, it may represent a risky surgical procedure in people who refuse blood products due to their religious beliefs, such as Jehovah’s Witnesses (JW). Preoperative optimization protocols of these patients allow performing arthroplasties in a safer manner avoiding allogeneic blood transfusion. Methods In our retrospective study, 2 groups of patients were evaluated. Group 1, included JW patients who underwent a preoperative Hb optimisation programme; group 2 included non-JW patients authorizing transfusion in case of necessity. Results Differences in Hb levels were: before surgery (JW 13,63±1,26 vs. non-JW 12,83±1,21, p-value=0,22), after surgery (day 1 Hb: JW 12,26±1,47 vs. non-JW 10,88±1,87, p-value=0,1; day 3 Hb: JW 10±2,97 vs. non-JW 9,23±1,07 p-value=0,64). In the JW group the mean Hb concentration decreased from 13,63±1,26 g/dL preoperatively to 12,26±1,47 g/dL (day 1) while in non-JW group fell from 12,83± g/dL to 10,88± g/dL. There was no statistically-difference between the 2 groups. Moreover, cost-effectiveness strategies were evaluated in both groups. Conclusion Our findings support that PBM programs represent a safe and good strategy in knee prosthetic surgery, decreasing costs, risks and transfusion overuse.