Background: Laparoscopic splenectomy (LS) is considered the gold standard for the treatment of hematologic disease of the spleen. Intraoperative bleeding is the main complication and main cause of conversion during LS. In this paper, we present our experience with 112 LS procedures, comparing two different techniques and instruments for spleen dissection and hilar vascular control. Methods: We have performed a total of 112 LS procedures in 9 years in two affiliated university hospitals. There were 48 males and 64 females (median age, 32.8 years). Indications were as follows: idiopathic thrombocytopenic purpura (ITP) in 42 patients, hereditary spherocitosis in 28, 6 with β-talassemia, 1 with hemolitic anemia, 27 with lymphoma, 2 with leukemia, 3 with splenic cysts, and 3 PPT cases. Associated procedures were present in 25 cases (17 cholecystectomy and 4 liver/lymphnodal biopsies + lysis of adhesions). Patients were divided in two groups according to the method of dissection and hilar section (group 1, endostapler + monopolar coagulation with 38 patients; group 2, the Ligasure^™ Vessel Sealing System (Valleylab, Boulder, CO) with 74 patients). Results: Groups were well matched according to age, indications, spleen sizes, and procedures associated. Conversion rates (10 cases, 9%; 5 in each group), postoperative hospital stay (median 4 days in each group), and intra- and postoperative complications were similar in the 2 groups without any mortality in each group, while intraoperative blood loss (loss of 100 mL in 55 patients in group 2, 78%; and in 21 patients in group 1, 52%), transfusion rates (8 patients in group 1 versus 4 patients in group 2), and operative mean time (150 minutes in group 1 versus 125 minutes in group 2) were minor in the Ligasure Vessel Sealing System group, with a statistical significance. Conclusions: The approach to spleen dissection and hilum section was safe and efficacy in each case, otherwise the use of Ligasure results in a gain of time. Furthermore the average intraoperative bleeding and average transfusion rates of this series were lower in group 2.