Aim: The purpose of this retrospective review of the charts of 51 Jehovah’s Witness patients, who underwent surgery without blood transfusions, was to compare two study groups (major surgery vs minor-medium surgery). Methods: We compared the following variables: age, sex, length of stay, type of surgical operation, use of intraoperative red cell salvaging devices, hemodilution, number of drainages and their stay, postoperative blood loss, complications, need of reoperation and mortality rate. Between medical variables we focused on blood production therapy and nutritional support (administration of iron, folate, erythropoietin and albumin) and blood tests (at the first day of admission; intraoperative; at the first postoperative day; at the discharge). Results: In the two study groups, we detected statistically significant differences in the following variables: total of postoperative blood loss (p <0.00001), complications rate (p = 0.0122) and in Hgb values (intraoperative: p = 0.0197; at the first postoperative day: p = 0.0028; at the discharge: p = 0.0100). Discussion: The aims of a bloodless surgery program are: 1) minimize blood loss, reducing iatrogenic anemia and intraoperative hemorrhage loss; 2) maximize blood production by administration of erythropoietin, iron and folate; 3) maximize cardiac output by alternatives to blood transfusions, as crystalloids, colloids and blood substitutes; 4) increase oxygen content; 5) decrease metabolic rate. We focused on advantages and disadvantages of the suggested procedures. Most interesting techniques are the normovolemic hemodilution and the intraoperative red cell salvaging devices, indispensable in emergency. Conclusions: A close team-work between surgeons, anesthesiologists and hematologists is determinant in a reference center that guarantees experience, organization, professionality, respect for the patients’ will and, above all, low morbidity and mortality rates, as those reported by our series.