Background: There are some difficulties regarding the evaluation of the post-splenectomy state. Objective: The objective of the study is to compare the post-splenectomy blood changes of immune thrombocytopenia (ITP) patients with those of trauma patients, 1 month and >_ 6 months after surgery. Methods: Medical records of patients, who had undergone total splenectomy for ITP and trauma at a tertiary center between January 2009 and December 2019, were retrospectively reviewed. Results: The current study included 52 patients, who had undergone splenectomy for ITP (57.7%), and trauma (42.3%). Splenectomy, irrespective of the indications, resulted in an increase in hemoglobin concentration, hematocrit, and platelet levels. Neutrophils were responsible for the preoperative leukocytosis in ITP patients, and neutrophilia was ameliorated by splenectomy and also withdrawal of the steroid therapy in some patients. Decreased neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio supported the finding that splenectomy ameliorated inflammation in ITP patients. Splenectomy resulted in a change in percentages of leukocytes in favor of basophils in ITP patients. Conclusions: Splenectomy, irrespective of the indications, resulted in an increase in hemoglobin concentration, hematocrit and platelet levels, lymphocyte, monocyte, and eosinophil counts. Splenectomy ameliorated inflammation in ITP patients and resulted in a change in percentages of leukocytes in favor of basophils.